Novel cyclopropanecarboxylic acids and esters

ABSTRACT

NOVEL CYCLOPROPANECARBOXYLIC ACIDS AND ESTERS OF THE FORMULA   Z2-C(-Z1)&lt;(-CH(-CO-R)-A-)   WHEREIN Z1 AND Z2 ARE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL, ARALKYL, ARYL, ALKENYL NON-CONJUGATED WITH THE CYCLOPROPANE RING, ALKYNYL NON-CONJUGATED WITH THE CYCLOPROPANE RING, CYCLOALKYL, CYCLOALKENYL AND HETEROCYCLIC; R IS SELECTED FROM THE GROUP CONSISTING OF OH AND OR&#39;&#39; IN WHICH R&#39;&#39; IS SELECTED FROM THE GROUP CONSISTING OF LOWER ALKYL WHICH MAY BE SUBSTITUTED, BENZYL WHICH MAY BE SUBSTITUTED ON THE PHENYL OR METHYLENE PORTION, N-METHYLENE-DICARBOXIMIDE, (5-BENZYL-FURYL-3) METHYL, AND A CYCLOPENTENE OF THE FORMULA   1-(O=),2-R&#34;,3-(CH3-)-2-CYCLOPENTEN-4-YL   WHEREIN R&#34; IS SELECTED FROM THE GROUP CONSISTING OF ALKYL, ALKYNYL, ALKENYL, ARYL, ARALKYL, CYCLOALKYL, CYCLOALKENYL AND HETEROCYCLIC; A IS A BIVALENT ALKYL RADICAL SELECTED FROM THE GROUP CONSISTING OF   R2-C(-R3)=CH-C(-R1)&lt; (A) (-Y=C(-R5)-C(-R4)=CH-)&gt;C&lt; (B)   (-Y&#39;&#39;=C(-R5)-C(-R4)=CH=)&gt;C&lt; (C)   WHEREIN R1 IS SELECTED FROM THE GROUP CONSISITING OF HYDROGEN AND LOWER ALKYL, R2 AND R3 ARE SELECTED FROM THE GROUP CONSISTING OF ALKYL, ALKYNYL, ALKENYL, ARYL, ARALKYL, CYCLOALKYL, CYCLOALKENYL AND HETEROCYCLIC AND TAKEN TOGETHER WITH THE CARBON ATOM TO WHICH THEY ARE ATTACHED FORM A RING SELECTED FROM THE GROUP CONSISTING OF CARBON HOMO RINGS AND UNSATURATED CARBON HOMO RINGS OF 3 TO 7 CARBON ATOMS AND HETEROCYCLIC RINGS WHICH MAY BE SUBSTITUTED WITH LOWER ALKYL OR LOWER ALKOXY AND R2 AND R3 MAY TOGETHER FORM A POLYCYCLIC AROMATIC RADICAL, R4 IS LOWER ALKYL, R5 IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN AND LOWER ALKYL AND R4 AND R5 TOGETHER WITH THE CARBON ATOMS TO WHICH THEY ARE ATTACHED MAY FORM A SATURATED OR UNSATURATED CARBON HOMO RING OR A HETEROCYCLIC RING, Y IS SELECTED FROM THE GROUP CONSISTING OF METHYLENE AND A SATURATED OR UNSATURATED CARBON CHAIN AND Y&#39;&#39; IS SELECTED FROM THE GROUP CONSISTING OF METHINE AND A SATURATED OR UNSATURATED CARBON CHAIN WITH THE PROVISO THAT WHEN Z1 AND Z2 ARE METHYL AND R1 IS HYDROGEN, R2 IS OTHER THAN METHYL AND THEIR PREPARATION.

United States Patent US. Cl. 260-240 R 6 Claims ABSTRACT OF THEDISCLOSURE Novel cyclopropanecarboxylic acids and esters of the formula\A/ I wherein Z, and Z are selected from the group consisting ofhydrogen, alkyl, aralkyl, aryl, alkenyl non-conjugated with thecyclopropane ring, alkynyl non-conjugated with the cyclopropane ring,cycloalkyl, cycloalkenyl and heterocyclic; R is selected from the groupconsisting of OH and OR in which R is selected from the group consistingof lower alkyl which may be substituted, benzyl which may be substitutedon the phenyl or methylene portion, N-methylene-dicarboximide,(S-benzyl-furyl-S) methyl,

and a cyclopentene of the formula 0 i Ia wherein R" is selected from thegroup consisting of alkyl, alkynyl, alkenyl, aryl, aralkyl, cycloalkyl,eycloalkenyl and heterocyclic; A is a bivalent alkyl radical selectedfrom the group consisting of wherein R is selected from the groupconsisting of hydrogen and lower alkyl, R, and R are selected from thegroup consisting of alkyl, alkynyl, alkenyl, aryl, aralkyl, cycloalkyl,cycloalkenyl and heterocyclic and taken together with the carbon atom towhich they are attached form a ring selected from the group consistingof carbon homo'rings and unsaturated carbon homo rings of 3 to 7 carbonatoms and heterocyclic rings which may be substituted with lower alkylor lower alkoxy and R and R may together form a polycyclic aromaticradical, R, is lower alkyl, R is selected from the group consistingofhydrogen and lower alkyl and R and R together with the carbon atoms towhich they are attached may form a saturated or unsaturated carbon homoring or a heteroice cyclic ring, Y is selected from the group consistingof methylene and a saturated or unsaturated carbon chain and Y' isselected from the group consisting of methine and a saturated orunsaturated carbon chain with the proviso that when Z and Z; are methyland R is hydrogen, R is other than methyl and their preparation.

PRIOR APPLICATION This application is a continuation-in-part of ourcopending, commonly-assigned US. patent applications Ser. No. 662,278,filed Aug. 22, 1967, and No. 879,942, filed Nov. 25, 1969, now bothabandoned.

OBJECTS OF THE INVENTION It is an object of the invention to provide thenovel cyclopropanecarboxylic acids and esters of Formula I.

It is another object of the invention to provide a novel process for thepreparation of the compounds of Formula I.

It is an additional object of the invention to provide novelinsecticidal compositions having low toxicity to warm blooded animals.

These and other objects and advantages of the invention will becomeobvious from the following detailed description.

THE INVENTION The novel cyclopropanecarboxylic acids and esters of theinvention have the structure of Formula I and are important compounds.The free acids (where R=OH) can be esterified with or converted into afunctional derivative thereof which can be esterified with, an alcoholof the formula HOR' to obtain the corresponding esters which haveinsecticidal properties and an anthelmintic activity.

The preferred compounds of the invention are a racemic oroptically-active cyclopropanecarboxylic derivative having the formula:

Z COT II R: I

wherein Z and Z, are selected from the group consisting of lower alkylhaving from 1 to 7 carbon atoms and phenyl and Z and Z togetherrepresent an alkylene residue having 4 to 5 carbon atoms, T is selectedfrom the group consisting of hydroxyl, chlorine and OT, T being selectedfrom the group consisting of alkali-metal anions, anions of opticallyactive organic bases, lower alkyl, (5-benzylfuryl-3)- methyl, and2-T"-3-methyl-1 oxo 2 cyclopentene-4-yl (T" is selected from the groupconsisting of lower alkenyl, cycloalkenyl of 3 to 7 carbon atoms, andfurfuryl) R and R are selected from the group consisting of lower alkyland phenyl and may together represent an alkylene residue having 3 to 7carbon atoms which may be interrupted by an heteroatom and which may besubstituted by at least one substituent selected from the groupconsisting of lower alkyl and lower alkoxy R' is selected from the groupcon sisting of hydrogen and lower alkyl or form together with R analkylene residue which may be unsaturated or substituted by a carbonchain with the proviso that when Z and Z are methyl and R is hydrogen, Ris other than methyl. Most preferred are compounds wherein R is hydrogenin trans configuration in relation to the carboxylic chain and R and Rtogether form a butylidene chain.

The esters of Formula I in which R is 2-R"-3-methyl-1-oxo-2-cyclopentene-4-yl wherein R has the above defini tion areparticularly distinguished by a strong insecticidal activity and a lowtoxicity to humans and warm blooded animals. Examples of said esters arethose wherein R" is allyl, cis-2-butenyl, cis-2,4-pentadienyl,2-cyclopentenyl, cyclohexyl, 2-cyclohexenyl, Z-propynyl and2-furylmethyl.

The following esters of Formula I have been found to possess a markedinsecticidal activity: the d,l-allethrolone esters of d, l-trans3,3-dimethyl 2 (2-ethyl- '-butenyl)- cyclopropanecarboxylic acid, d,l-trans 3, 3-dimethyl-2 cyclopentylidenemethyl cyclopropanecarboxylicacid, d, l-trans 3, 3-dimethyl 2cyclohexylidenemethyl-cyclopropanecarboxylic acid, d, l-trans3,3-dimethyl-2cyclopropylidene-methyl 1 cyclopropanecarboxylic acid andd,l-trans 3,3dimethyl-2-cyclobutylidenemethyl l cyclopropanecarboxylicacid; the cis-cinerolone ester of d, ltrans3,3-dimethyl-2-cyclopenylidenemethyl 1 cyclopropanecarboxylic acid; the1-oxo-3-methyl-2-(2'-cyclohexenyl)-2-cyclopentene-4-ol ester ofd,1-trans 3,3-dimethyl-2- cyclopentylidenemethyl cyclopropanecarboxylicacid; and the (5-benzyl-furyl-3 )methyl alcohol ester of d,1- andd-trans 3,3-dimethyl-2-cyclopentylidene-methyl 1 cyclo propanecarboxylicacid. The said esters have been found to be effective against suchinsects as house flies, grain weevils, American cockroaches, Germancockroaches, yellow fever mosquitos as dosages depending on the way theyare used. More particularly they may be associated with synergists suchas piperonyl butoxide and spread by means of aerosols, space-sprays orpowders.

The novel process of the invention comprises reacting an alkali metalaryl sulfinate of the formula ArSO M II wherein M is an alkali metalsuch as sodium or potassium and Ar is an aryl radical of l to 2 aromaticrings which may be substituted with at least one substituent selectedfrom the group consisting of lower alkyl, lower alkoxy, halogen, nitroand halo methyl with an allylic halogen derivative of the formula a;

HAX IH wherein A has the above definition and X is selected from thegroup consisting of chlorine, iodine, bromine, mesyl and tosyl to formthe corresponding aryl allyl sulfone of the formula wherein A and Arhave the above definitions, reacting the latter in the presence of abasic agent with an a,p-ethylenic ester of the formula wherein Z and Zhave the above definition and R' is a substituted or unsubstituted loweralkyl radical to form an ester of the formula wherein A, R'", Z and 2,have the foregoing definition, hydrolyzing the latter under alkalineconditions to form the corresponding free acid, preferably convertingthe latter into a functional derivative such as acid halide, anhydride,mixed anhydride, ester or metal salt, reacting the functional derivativeor the free acid with an alcohol of the formula wherein R has theforegoing definition and N is selected from the group consisting ofhydroxy and halide to form the corresponding ester of Formula I.

A preferred embodiment of the process for the preparation of a compoundof the formula:

Z CO-T;

wherein M is an alkali-metal and Ar is an aryl radical having 1 to 2aromatic rings which may be substituted with at least one substituentselected from the group consisting of lower alkyl, lower alkoxy,halogen, nitro and halomethyl, with an allylic halide having theformula:

wherein R is selected from the group consisting of hydrogen and loweralkyl or form together with R: an alkylene residue which may beunsaturated or substituted by a carbon chain, X is selected from thegroup consisting of chlorine, bromine, iodine, methyl sulfonyloxy,p-toluenesulfonyloxy and hydroxywith the proviso that when X is OH, thereaction is performed in the presence of formic acid-and R and R havethe above defined meanings, to form the corresponding arylalkylsulfoneof the formula:

wherein the substituents R, R R and Ar have the same meanings as aboveand reacting the said sulfone with the ester of a m,p-unsaturatedaliphatic carboxylic acid of the formula:

o=oH-oo,R"

wherein Z and Z are defined as above and R" is a lower alkyl to form thecorresponding ester of a cyclopropyl carboxylic acid of the formula:

Z O 0 OR" wherein Z, Z R, R R and R" are defined as above, saponifyingthe latter under alkaline conditions if desired to form thecorresponding racemic cyclopropane carboxylic acid, resolving the latterif desired with an optically active organic base, converting the saidracemic or opticallyactive acid into a functional derivative selectedfrom the group consisting o f,,acid chloride, acid bromide, anhydride,mixed anhydride, esters and salts thereof, and reacting the saidfunctional derivative with a compound of the formula T-X wherein X' ishydroxy or halogen and T has the above-definition, and recovering thedesired ester.

The process of the invention has the advantage of simplicity since itsynthesizes a substituted cyclopropane in a single step from readilyavailable raw materials or from materials which can be prepared withoutany great difficulty and the process can be operated without anyhazards. Known methods of producing cyclopropanecarboxylic acids ortheir esters require the preparation and use of relatively unstablediazo compounds such as diazoacetonitrile or diazioacetic acid esters orto avoid this hazard required a multiple step process having rather pooryields in some steps.

Another advantage of the process of the invention is the general naturethereof whereby a large variety of differently substituted compounds maybe made. In the aryl allyl sulfones of Formula IV, for example, the arylgroup may be homo or polycyclic and may be substituted with numerousdifferent substituents, the p-tolyl group furnishing particularlyexcellent results. More important, the allyl group of the aryl allylsulfone can have most varied structures and may be of the linear typesuch as \C=CH-CH:

Rs wherein R and R may be, for example, ethyl, isopropyl, phenyl,cycloalkyl or together may form a 5 carbon ring or a heterocyclic or thecyclic type such as wherein R may be alkyl.

The process of the invention is so general that the aryl allyl sulfoneof Formula IV may not only be reacted with an ester of Formula V butalso with other 0:,fi-CthYl6l1iC carbonyl compounds such as ketones,nitriles and conjugated amides to form the correspondingcyclopropanecarboxylic acid ester.

The preparation of the aryl allyl sulfones of Formula IV is preferablyeffected in a solvent such as a methanol or ethanol medium in thepresence of a basic agent such as alkali metal carbonates or acetates.Preferably, the said reaction is effected in methanol in the presence ofsodium or potassium carbonate.

As a modification of the process, the aryl allyl sulfones can beprepared by reacting an alkali metal aryl sulfinate with an alcohol ofthe formula H-A-OH wherein A has the above definition in the presence offormic acid or by the method described in French Pat. No. 1483715.

The alkali metal aryl sulfinates of Formula H can be prepared by knownprocess such as reduction of aryl sulfonyl chlorides to aryl sulfinicacids which are converted into the corresponding alkali metal salts. Theacrylic acid esters of Formula V are prepared also by known methods andare preferably the lower alkyl esters such as methyl, ethyl or n-butyl.

The reaction of the aryl allyl sulfone and the acrylic ester of FormulaV is effected in an anhydrous organic medium in the presence of a basicagent, preferably an alkali metal amide, hydride or alcoholate or dimsylsodium. Particularly advantageous basic agents are sodium methylate,sodium tert.-amylate and potassium tert.-butylate. The organic solventmay be selected from the group consisting of aromatic hydrocarbons suchas benzene, toluene, etc.; ethers such as tetrahydrofuran; andpreferably aprotic dipolar solvents such as dimethylformamide,dimethylsulfoxide, hcxamethylene-phosphoramide or acetonitrile. In themost preferred process the reaction is performed in tetrahydrofuran inthe presence of potassium tert.-butylate or in benzene in the presenceof sodium tert.-amylate or in dimethylformamide in the presence ofpotassium tert.-butylate or in dimethylsulfoxide in the presence ofsodium methylate or in dimethylsulfoxide in the presence of potassiumtert.-butylate.

An additional advantage of the process of the invention occurs when Ahas the structure When A has the structure C=CH Rs-C \C/ the compound ofFormula I being of the spiro type, the two theoretically possibleisomers can be isolated and these isomers have been designated as thecis isomer and the trans isomer. They may be represented as follows:

Trans isomer Cls isomer Z 1 Z i C O-R C O-R Although it is not necessaryto postulate the mechanism for the formation of thecyclopropanecarboxylic acid esters in which R is OR" from the aryl allylsulfone and the a,p-ethylenic ester, the reaction can be considered totake place in two steps. In the first step, the sulfone function of thecompound of Formula IV activates the methylene and methine group in thetat-position thereby inducing the 1,4-addition of the sulfone to theconjugated double bond of the said ester, nonwithstanding theunfavorable steric and electron effects of Z; and Z After protonation ofthe intermediate adduct, the formation of a compound of Formula VII wasascertained 0 0 VII which may actually exist in the basic and aproticreaction medium in the form of an u-carboalkoxylic anion or its enolform. In the second step which may occur simultaneously, the sulfonefunction of the intermediate of Formula VII or its a-carboalkoxylic orenol anion plays a new role due to its ability to be eliminated in theform of an ArSO -sulfinic anion thereby promoting the intramolec ularcyclization to form the cyclopropanecarboxylic acid ester in which R isOR'". However, the invention is not intended to be limited to the abovetheoretical considerations. Moreover, the invention covers the entireprocess where an intermediate of Formula VII or an analog is isolatedand then reacted to form the said cyclopropanecarboxylic acid ester.

The hydrolysis of the cyclopropanecarboxylic acid esters wherein R isOR"' to the free acids may be effected with an alkali metal hydroxidesuch as sodium hydroxide or potassium hydroxide and is usually efiectedin an aqueous alcohol medium such as methanol, ethanol or glycol.

The conversion of the free cyclopropanecarboxylic acids of Formula Iinto the esters where R is OR' can be obtained by various methods withreaction of the corresponding alcohol. The alcohol may be directlyreacted with the said acid in the presence of a strong acid catalyst,preferably with azeotrophic distillation of the water of reactionformed.

However, it may be advantageous to first convert the said free acid intoan acid function derivative such as its acid anhydride, a mixed acidanhydride, its acid chloride or a metal salt which can then be reactedwith the appropriate alcohol to obtain the desired ester of Formula LThe acid anhydride can be obtained by reaction of acetic acid anhydrideand the said free acid, for example.

The cyclopropanecarboxylic acid chloride can be formed by reacting thefree acid of Formula I with a chlorinating agent such as thionylchloride, phosphorus trichloride, phosphorus pentachloride, etc.Preferably, the said acid is reacted with thionyl chloride in a benzenemedium to form the acid chloride which is then reacted with theappropriate alcohol in an aromatic hydrocarbon solvent such as benzeneor toluene in the presence of a tertiary amine such as pyridine to bindthe hydrochloric acid formed.

-A metal salt of the cyclopropanecarboxylic acid of Formula I can beformed by neutralizing the said acid with an alcohol solution of alkalimetal alcoholate followed by removal of the solvent and the alkali metalsalt of the said acid can then be reacted with a. halogenatedderivative, preferably the bromine derivative, of the alcohol indimethylformamide to form the desired ester.

As a modification of the said process, the cyclopropanecarboxylic acidesters where R is OR" may be transesterified with the desired alcohol byheating tlie reactants in the presence of sodium while continuouslydistilling oil the freed lower alcohol. However, it is sometimesadvantageous for purification to saponify the said acid ester to formthe free acid, react the latter to form again a lower alkyl ester suchas with diazomethane to form the methyl ester and subjecting the latterester to trans-esterification with the desired alcohol.

In another modification of the process of the invention wherein R and Rare alkyl of 1 to 6 carbon atoms or taken together with the carbon atomto which they are attached form a cycloalkyl of 3 to 6 carbon atoms,racemic trans-3,3-dimethyl-2-formyl-cyclopropane-l-carboxylic acid or of(1R,2R) or (1S,2S) configuration, or an alkyl ester of these compoundsof Formula A:

in which R; and R have the afore-mentioned meaning. This phosphoniumsalt is able to exist in the basic medium in the form of an ylide, ofFormula B:

in order to obtain racemictrans-3,3-dimethyl-2-R'-cyclopropane-l-carboxylic acid or of (1R,2R) or(lS,2S) configuration, or an alkyl ester of these compounds of Formula-Ia of the same configuration at 1 and at 2 as the starting compoundwherein R and R have the afore-mentioned meaning, and hydrolyzing thecondensation product with an alkaline agent when R is an alkyl of 1 to 4carbon atoms to isolate the corresponding racemic3,3-dimethyl-2-R'-cyclopropane-l-carboxylic acid or of (1R,2R) or(1S,2S) configuration, of Formula Ib HaC COOH Hzc o u H wherein R hasthe afore-mentioned meaning.

Among the phosphonium salts of Formula B, which are condensed with theacid or ester of Formula A are salts of triaryl phosphonium,specifically salts of triphenylphosphonium, salts of tris (dialkylamino)phosphonium, of [(bisdialkyamino)-aryl] phosphonium and of(dialkylamino-diaryl) phosphonium which all give rise to an ylide of theFormula B under the action of strong bases. As the phosphonium salt, theiodide and bromide are preferred.

Among the strong bases, in the presence of which condensation of thephosphonium salt of Formula B with the aldehyde of Formula A iselfected, one can mention specifically alkali metal hydrides, alkalimetal amides, alkali metal alcoholates or alkyl lithiums.

Condensation of the aldehyde of Formula A with the phosphonium salt ofFormula -B is conveniently elfected in an organic solvent such asdiethylene glycol monomethyl ether, diethyleneglycol diethyl ether,ethyl ether, dimethyl sulfoxide, dimethyl-forrnamide, tetrahydrofuran,dimethoxyethane or benzene. Excellent results may be obtained by the useof an alkali metal alcoholate in the presence of dimethylsulfoxide or ofan alkyl lithium in the presence of dimethoxyethane or benzene.

After condensation of the ylide of Formula B with the aldehyde ofFormula A, the crude reaction product is purified by conventionalmethods. For example, the product can be treated with reagent T ofGirard to eliminate by solubilization in the aqueous phase the unreactedaldehyde fraction or purified by pasting or crystallization from asuitable solvent. When the starting aldehyde of Formula A is an ester,the crude reaction product can be purified by rectification.

The cyclopropyl or cyclobutyl triaryl phosphonium halide is preferablycyclopropyl or cyclobutyl tri-phenyl phosphonium halide. The basic agentused to etfect the condensation of the cyclopropyl or cyclobutyl triarylphosphonium halide with dl-trans caronaldehyde acid is preferably analkali metal hydride such as sodium or potassium hydride and thecondensation is preferably conducted in a medium of dimethoxyethane ordimethoxypropane. Other bases such as alkali metal amides and othersolvents such as tetrahydrofuran may be used.

The preparation of cyclopropyl triphenyl phosphonium bromide by thermaldecomposition of 3-(2-oxotetrahydrofuranyl) triphenyl phosphoniumbromide is described by H. Hartung (Angew. Chem. Int. Ed. 4, page 704(1965)). The preparation of cyclobutyl triphenyl phosphonium bromide bycyclization of 4-bromobutyl triphenyl phosphonium bromide is describedby A. Mondon, Ann. 603, (1957). Other cyclopropyl and cyclobutyl triarylphosphonium halides can be prepared by similar processes. dl-transcaronaldehyde acid (or dl-trans 3-f0rmyl-2,2-

9 dimethyl-cyclopropanecarboxylic acid) can be prepared by the methoddescribed by M. Matsui et al. [Agr. Biol. vol. 27, No. 8, pages 554-557(1963)].

The 2-R"-3-methyl-l-oxo-2-cyclopentene-4-ol wherein R has the abovedefinition, may be prepared by the process described in I.A.C.S., vol.71 (1949), p. 1,517 or modification of this process or by degradation ofnatural products.

Racemic mixtures of the cyclopropanecarboxylic acids of Formula I can beresolved with optically active organic bases such as ephedrine, ifdesired.

The cyclopentenolone esters of Formula I prepared by the process of theinvention as a rule consist of a mixture of diastereoisomers. Forexample, the ester obtained by esterification of a d,l-transcyclopropanecarboxylic acid of Formula I when R is OH withdl-allethrolone may consist of four diastereoisomers forming tworacemates in varying pro ortions: one racemate consists of the ester ofthe -trans acid with -allethrolone and of the ester of the -trans acidwith -allethrolone and the second racemate consists of the ester of the-trans acid ester with -allethrolone and of the ester of -trans acidwith -allethrolne. As another example, the ester obtained by startingwith a dl-trans cyclopropanecarboxylic acid of Formula I and -cineroloneconsists of two diastereoisomers: the ester of the -trans acid with-cinerolone and the ester of the -trans acid with -cinerolone.

0 preferred group of compounds of Formula I are those compounds whereinZ and Z, are selected from the group consisting of hydrogen; lower alkylof 1 to 7 carbon atoms such as methyl, ethyl, propyl, n-butyl; phenylwhich may be substituted; phenyl lower alkyl; lower alkenylnonconjugated with the cyclopropyl ring; lower alkynyl nonconjugatedwith the cyclopropyl ring; cycloalkyl and cycloalkenyl of 3 to 7 carbonatoms such as cyclopentyl, cyclohexyl, cyclohexenyl, etc.; andheterocyclic such as furyl; R is selected from the group consisting oflower alkyl which may be substituted such as methyl, ethyl, halo ethyl,etc.; benzyl which may be substituted on the methylene with a loweralkyl or on the phenyl with halogen, lower alkyl, lower alkoxy, halolower alkyl, lower alkenyl, etc.; N-methylene dicarboximides; 2-R"- 3-methyl-1-oxo-2-cyclopentene-4-yl wherein R" is selected from the groupconsisting of lower alkyl such as methyl; lower alkenyl such as allyl,butenyl, pentadienyl; alkynyl such as ethynyl; phenyl which may besubstituted; phenyl lower alkyl; cycloalkyl and cycloalkenyl of 3 to 7carbon atoms such as cyclohexyl, cyclopentenyl, cyclohexenyl;heterocyclic such as furfuryl; and (-benzyl-furyl-3)- methyl; R and Rare selected from the group consisting of lower alkyl, lower alkynyl,lower alkenyl, phenyl lower alkyl, phenyl which may be substituted,cycloalkyl and cycloalkenyl of 3 to 7 carbon atoms which may besubstituted with lower alkyl and/or lower alkoxy and R and R togethermay form a polycyclic radical such as fluorene or together with thecarbon atom towhich they are attached may form a cycloalkyl,cycloalkenyl and heterocyclic of 3 to 7 carbon atoms such ascyclohexenyl, cyclopentadienyl which may be substituted with lower alkyland/or lower alkoxy; R is lower alkyl such as methyl; R is hydrogen orlower alkyl and R and R together with the carbon atoms to which they areattached form a cycloalkyl, cycloalkenyl or heterocyclic of 3 to 7carbon atoms; Y is methylene and Y' is methine.

In the following examples there are described several preferredembodiments to illustrate the invention. However, it should beunderstood that the invention is not intended to be limited to thespecific embodiments.

PREPARATION OF REACTANTS (I) Preparation of 3-ethyl-1-pentene-3-ol Asolution of 93 gm. of 3-pentanone in 100 cc. of tetrahydrofuran wereintroduced over one hour into 615 10 cc. of a solution of vinylmagnesium chloride in tetrahydrofuran titrating 1.78 moles/liter underan atmosphere of nitrogen and at a temperature not above 50 C. Themixture was agitated at room temperature for 15 hours. Thereafter, thereaction mixture was cooled to 0 C. and 500 cc. of water were addedunder vigorous agitation and at a temperature not exeeding '+40 C. Theorganic phase was separated by decantin and after the aqueous phase wasextracted with ether the organic phases were combined and dried overmagnesium sulfate. Then the solvents were eliminated and the residueobtained was rectified under atmospheric pressure, to obtain gm. of3-ethyl-l-pentene-3-ol having a boiling point of 131 C.l32 C. and arefractive index n =1.4345, which was utilized as such for thepreparation of 1- bromo-3ethyl-2-pentene.

Working in the same fashion, but starting with 4-heptanone,3-propyl-1-hexene-3-ol having a boiling point of 64-68 C. under 14 mm.Hg and a refractive index n =l.438 was obtained.

By starting with 2,4-dimethyl-pentane-3-one,3-isopropyl-4-methyl-1-pentene-3-ol having a boiling point of 71- 75 C.under 30 mm. pressure of mercury and a refractive index n =l.443 wasobtained.

By starting with 2,6-dimethyl-4-heptanone, 3-isobutyl-S-methyl-l-hexene-S-ol having a boiling point of 87 C. under 20 mm.pressure of mercury and a refractive index n =1.4395 was obtained. Thiscompound is not described in the literature.

By starting with benzophenone, l,l-dipheny1-2-propenel-ol having aboiling point of 1l0 C. under 0.04 mm. pressure of mercury and areflective index was obtained. This compound is not described in theliterature.

By starting with 4,4-dimethyl-cyclohexane-l-one, 1-vinyl-4,4-dimethyl-cyclohexane-1ol having a boiling point of 9396 C.under 20 mm. pressure of mercury was obtained. This compound is notdescribed in the literature.

By starting with 3,3,5,S-tetramethyl-cyclohexane-l-one,3,3,5,5-tetramethyl-l-vinyl-cyclohexane-l-ol having a boiling point of98 C. under 18 mm. pressure of mercury and a refractive index n =1.467was obtained.

By starting with 2,3,5,6-tetrahydropyrane-4-one, 2,3,5,6-tetrahydro-4-vinyl-pyrane-4-ol having a boiling point of 97100 C.under 21 mm. pressure of mercury and a refractive index n =l.473 wasobtained. This compound is not described in the literature.

By starting with cyclobutanone, l-vinyl-cyclobutanel-ol having a boilingpoint of 4650 C. under 17 mm. pressure of mercury and a refractive indexn =1.4590 was obtained. This compound is not described in theliterature.

(II) Preparation of 1-bromo-3-ethyl-2-pentene A solution of 19.1 cc. ofphosphorus tribromide in cc. of petroleum ether (boiling point of 5070C.) was introdued within 1 hour and at a temperature of about 20 C. intoa mixture of 64 gm. of 3-ethyl-1- pentene-3-ol and cc. of petroleumether (boiling point=50-70 C.). The reaction mixture was agitated for 1hour and 30 minutes at 10 C. and then it was poured into a mixture ofsalt water and ice. The organic phase was decanted, washed first with anaqueous sodium bicarbonate solution and then with an aqueous sodiumchloride solution. The combined aqueous phases were reextracted withpetroleum ether and the re-extractions were combined with the principalorganic solution. The solution thus obtained was dried over magnesiumsulfate, filtered and dried. The solvent was removed under normalpressure in the presence of potassium carbonate in an inert atmospherein an apparatus provided with a rectifying column. The resultant residuewas then rectified under reduced pressure in the presence of potassiumcarbonate and in an inert atmosphere to obtain 87.175 gm. of1-bromo-3-ethyl-2-pentene having a boiling point of 74 C. under 28 mm.pressure of mercury. This product was utilized as such for the nextstep. It was maintained in an inert atmosphere in the presence ofpotassium carbonate. Working in the same fashion, but starting with3-propyl-1-hexene-3-ol, 1-bromo-3-propyl-2-hexene having a boiling pointof 85 90 C. under 17 mm. pressure of mercury and a refractive index n=l.483 was obtained.

By starting with 3-isopropyl-4-methyl-1-pentene-3-ol,l-bromo-3-isoproyl-4-methyl-2-pentene having a boiling point of 92 C.under 32 H1. pressure of mercury and a refractive index n =1.479 wasobtained. This compound is not described in the literature.

By starting with 3-isobutyl-5-methyl-1-hexene-3-ol, 1-bromo-3-isobutyl-S-methyl-Z-hexene with a boiling point of 7076 C. under1 mm. pressure of mercury and a refractive index n =L4750 was obtained.

This compound is not described in the literature.

By starting with 2,6-dimethyl-l-vinyl-cyclohexane-l-ol,1-brorno-2-(2',6'-dimethylcyclohexylidene)-ethane having a boiling pointof 115 -120 C. under 20 mm. pressure of mercury was obtained. Thiscompound is not described in the literature.

By starting with 1-vinyl-4,4-dimethylcyclohexane-l-ol,1-bromo-2-(4,4-dimethylcyclohexylidene) ethane having a refractive indexn =1.5060 was obtained. This compound is not described in theliterature.

By starting with 3,3,5,5 tetramethyl-l-vinyl-cyclohexane-l-ol, l-bromo 2(3',3',5 -tetramethyl-cyclohexylidene)-ethane having a boiling point of87 C. under 0.5 mm. pressure of mercury and a refractive index n =1.505was obtained.

By starting with 2,3,5,fi-tetrahydro-4-vinyl-pyran-4-ol, 1 bromo 2(2',3',5', '-tetrahydro-4'-pyrany1idene) ethane having a boiling pointof 73 C. under 1.5 mm. pressure of mercury and a refractive index n=1.529 was obtained. This compound is not described in the literature.

By starting with l-vinyl-cyclobutane-l-ol, 1-bromo2-cyclobutylidene-ethane with a boiling point of 56 58 C. under 15 mm.pressure of mercury and a refractive index n =1.5160 was obtained. Thiscompound is not described in the literature.

By starting with 1,1-diphenyl-2-propene-l-ol, l-bromo-3,3-diphenyl-2-propene having a melting point of 43 C. was obtained.This compound is not described in the literature.

(III) Preparation of 3-methyl-2-cyclohexene-l-ol 8.25 gm. of lithiumaluminum hydride were introduced under an atmosphere of nitrogen into100 cc. of tetrahydrofuran and at a temperature of C. a solution of 33gm. of 3-methyl-2-cyclohexene-l-one obtained according to the methoddescribed by Klaze [Ann. 281,94 (1894)], in 35 cc. of tetrahydrofuranwere added thereto within the space of about 45 minutes. The reactionmixture was agitated at room temperature for 1 hour. The excess hydridewas decomposed by addition of ethyl ether saturated with water and thenby addition of water. The precipitate thus formed was eliminated byfiltration and the filtrate obtained was dried over magnesium sulfateand concentrated to dryness to obtain 31.85 gm. of raw 3-methyl-2-cyclohexene-l-ol which product was utilized as such for the next step.This product was a liquid with a refractive index of n =1.4785.

EXAMPLE I Preparation of dl-trans3,3-dimethyl-2-(2'-ethyl-l'-butenyl)cyclopropanecarboxylic acid and itsester with dlallethrolone Step A.Preparation of(3-ethyl-2-pentenyl)-phenylsulfone:

1.85 gm. of sodium carbonate and 18.5 gm. of sodium phenyl sulfinatewere introduced into 60 cc. of methanol.

Then 20 gm. of 1-bromo-3-ethyl2-pentene were added within the space ofabout 30 minutes at room temperature to the resulting suspension, whichthen was agitated for 1 hour and 30 minutes at room temperature. Thenthe reaction mixture was poured into ice-water and the organic phase wasseparated by decanting. The aqueous phase was extracted with ethyl etherand the ether extracts were combined with the principal organicsolution. The solution thus obtained was dried over magnesium sulfateand the solvent was removed under reduced pressure to obtain 21.665 gm.of (3-ethyl-2 pentenyl) phenylsulfone. A sample of this product wasrectified under reduced pressure and the boiling point was 125 C. under0.02 mm. pressure of mercury and its refractive index n =1.530.Analysis: C H SO molecular weight=238.34. Calculated (percent): C,65.53; H, 7.61; S, 13.46. Found (percent): C, 65.4; H, 7.6; S, 13.2.

This compound is not described in the literature.

Step B.Preparation of ethyl dl-trans 3,3-dimethyl-2-(2'-ethy1-1'-butenyl)cyclopropanecarboxylate:

39 gm. of potassium tert.-butylate titering 87% were dissolved in 240cc. of dimethylformamide and after 30 gm. of (3-ethyl-2-pentenyl)-phenylsulfone were introduced into this solution, it was then agitated for 15minutes. Next, 29.1 gm. of ethyl pgfi dimethylacrylate were introduceddropwise into the reaction mixture within the space of 10 minutes. Thismixture was then agitated for 2 hours at room temperature, cooledthereafter to 0 C., and poured into a mixture of ice and a diluteaqueous solution of hydrochloric acid. Then the reaction mixture wasextracted with ethyl ether and the ether solutions were combined, washedfirst with an aqueous solution of sodium chloride, then with an aqueoussolution of sodium bicarbonate and finally again with an aqueoussolution of sodium chloride. The ether solution was dried over magnesiumsulfate, concentrated to dryness under reduced pressure and thenrectified under reduced pressure to obtain 25.57 gm. of raw ethyldl-trans 3,3-dimethyl-2-(2'- ethyl-1'-butenyl)-cyclopropanecarboxylatehaving a boiling point of 70 C.-72 C. under 0.08 mm. pressure of mercuryand a refractive index n =1.462. This product was utilized as such forthe next step.

This product is not described in the literature.

Step C.Preparation of dl-trans-3,3-dimethyl-2-(2'- ethyl-lbutenyl)-cyclopropanecarboxylic acid:

20 gm. of raw ethyl dl-trans 3,3-dimethyl-2(2'-ethyl-1-butenyl)-cyclopropanecarboxylate were introduced into a mlxture of cc.of a 2 N methanolic sodium hydroxide solution and 20 cc. of water. Thereaction mixture was heated to reflux which was maintained for 1 hour.Then the methanol was eliminated under reduced pressure and theremainder was diluted with water. The aqueous phase was extracted withethyl ether and the ether extracts were combined. The ether solutionthus obtained was washed once with water. The aqueous wash waters werecombined with the principal aqueous phase, and all of the aqueous phasescombined were acidified with a dilute aqueous solution of hydrochloricacid. The acidified aqueous phase was extracted with methylene chlorideand the methylene chloride solution, as washed with water, dried overmagnesium sulfate and concentrated to dryness under reduced pressure.The residual oil was rectified under reduced pressure to obtain 11.95gm. of dl-trans 3,3-dimethyl-2-(2-ethy1-1-butenyl)-cyclopropanecarboxylic acid having a boiling point ofC. under 0.05 mm. of mercury pressure and melting point=3637 C. A sampleof this product, purified by rectification under reduced pressure, had aboiling point=94 C. under 0.01 mm. pressure of mercury and a meltingpoint=37 C. Analysis: C H O molecular weight=196.28. Calculated(percent): C, 73.42; H, 10.27. Found (percent): C, 73.5; H, 10.0.

This product is not described in the literature.

Step D.-Preparation of dl-trans 3,3-dimethyl-2-(2'-ethyl-1'-butenyl)-cyclopropanecarboxylic acid chloride:

5 gm. of dl-trans 3,3-dimethyl-2-(2'-ethyl-1-butenyl)-cyclopropanecarboxylic acid were introduced into 10 cc. of petroleumether (boiling point=50-70 C.) and after 2.8 cc. of thionyl chloridewere added, the mixture was agitated at room temperature for 1 hour and30 minutes. The petroleum ether and excess thionyl chloride wereeliminated by distillation and the residue was rectified under reducedpressure to obtain 5.25 gm. of dl-trans 3,3-dimethyl-2-(2' ethyl 1'butenyl)-cyclopropanecarboxylic acid chloride having a boiling point of68 under 0.2 mm. pressure of mercury. This product was utilized as suchfor the next step.

This product is not described in the literature.

Step E.Preparation of dl-trans 3,3-dimethyl-2-(2'-ethyl-1'-butenyl)-cyclopropanecarboxylate of dl-allethrolone:

5.25 gm. of dl-trans 3,3-dimethyl-2-(2-ethyl 1butenyl)-cyclopropanecarboxylic acid chloride were introduced into amixture of 30 cc. of benzene and 6 cc. of pyridine. Then a solution of3.7 gm. of dl-allethrolone in 5 cc. of benzene was added over about 10minutes and at a temperature of C. The reaction mixture was agitated forabout 15 hours at room temperature, after which the pyridinehydrochloride formed was eliminated by filtration. The organic phase waswashed first with a dilute aqueous hydrochloric acid solution, then withwater, next with an aqueous sodium bicarbonate solution and finallyagain with water. The solution thus obtained was dried over magnesiumsulfate and then concentrated to dryness under reduced pressure. Therecovered residue was subjected to chromatography through alumina withelution with cyclohexane to obtain 5.445 gm. of dl-trans3,3-dimethyl-2-(2'-ethyl- '-butenyl)-cyclopropanecarboxylate ofdl-allethrolone having a refractive index of n =1.4520. Analysis: C I-10 molecular weight=330.45. Calculated (percent): C, 76.32; H, 9.15.Found (percent): C, 76.1; H, 9.0.

This product is not described in the literature.

EXAMPLE n Preparation of dl-trans 3,3 dimethyl-2-(2'-isobutyl-4'- methyl1' pentenyl)cyclopropanecarboxylic acid and its ester withdl-allethrolone Step A.Preparation of (3-isobutyl 5methyl-Z-hexenyl)-phenyl-sulfone:

55 gm. of sodium phenyl sulfinate were dissolved in 500 cc. of methanoland then 8 gm. of potassium carbonate, 1 gm. of sodium iodide andfinally 71 gm. of 1-bromo-3-isobutyl-5-methyl-2-hexene were added to thesolution, which was then agitated for 15 hours at room temperature.Thereafter, the reaction mixture was concentrated to dryness underreduced pressure and water was added thereto. The aqueous phase wasextracted with methylene chloride and the methylene chloride extractswere combined. The organic solution thus obtained was washed with water,dried and concentrated to dryness under reduced pressure. The residuewas subjected to chromatography through an alumina column to obtain62.32 gm. of the (3-isobutyl-5-methyl-2-hexenyl)phenylsulfone. Thisproduct is not described in the literature.

Step B.--Preparation of methyl dl-trans 3,3-dimethyl-2-(2'-isobutyl-4'-methyl 1 pentenyl)-cyclopropanecarboxylate:

24.56 gm. of potassium tert.-butylate titering 87% were dissolved in 120cc. of dimethylformamide and 28 gm. of (3-isobutyl-S-methyl-Z-hexenyl)phenyl sulfone were added. The solution was agitated for 2 minutes andthen 18 cc. of methyl fl,fidimethylacrylate were introduced thereinwithin about minutes. The reaction mixture was agitated for 2 hours atroom temperature, then poured into a mixture of a dilute aqueoushydrochloric acid solution and water. The aqueous phase was extractedwith methylene chloride and the methylene chloride extracts werecombined and was successively washed with water, with an aqueoussolution of sodium bicarbonate and again 14 with water, then dried andconcentrated to dryness. The resultant residue was rectified underreduced pressure to obtain 24.68 gm. of the desired methyl dl-trans3,3-dimethyl-2-(2'-isobutyl-4'-methyl 1'pentenyl)-cyclopropanecarboxylate, having a boiling point of 113 C.under 1 mm. pressure of mercury.

This product is not described in the literature.

Step C.Preparation of dl-trans3,3-dimethyl-2-(2-isobutyl-4'-methyl-1'-pentenyl)-cyclopropanecarboxylicacid:

18 cc. of a 10 N aqueous sodium hydroxide solution were introduced intoa mixture of cc. of methanol and 10 cc. of water. The solution was thenbrought to reflux under a current of nitrogen and reflux was maintainedfor 10 minutes after which a solution of 24.6 gm. of methyl dl-trans3,3-dimethyl-2-(2'-isobutyl-4'-methyl-'-pentenyl)-cyclopropanecarboxylate in 30 cc. of methanol was added. Thereaction mixture was agitated for 1 hour at reflux after which water wasadded and the methanol was eliminated. Then the reaction mixture wascooled and the aqueous phase was extracted with ethyl ether. The etherextracts were combined and washed with water. The wash waters werecombined with the principal aqueous phase and the ether solutioncontaining the neutral fraction was eliminated.

The combined aqueous phases were acidified with a dilute aqueoushydrochloric acid solution and the acid aqueous phase was extracted withether. The ether extracts were combined, washed with water, dried andconoenrtrated to dryness. The residue obtained was crystallized frompetroleum ether (boiling point=35-70 C.) and then from a mixture ofisopropyl ether and petroleum ether, (boiling point=35-70 C.) to obtainthe desired dl-tnans 3,3 dimethyl 2(2'-isobutyl-4'-methyl-lpentenyl)cyclopropaneoarboxylic acid having amelting point of 74 C. Analysis: C H 0 molecular weight= 252.38.Calculated (percent): C, 76.14; H, 11.18. Found (percent): C, 76.1; H,10.9.

This product is not descn'bed in the literature.

Step D.Preparation of dl-trans 3,3-dimethyl-2-(2'- isobutyl 4'methyl-1'-pentenyl)-cyclopropaneoarboxylic acid chloride:

8 gm. of dl-trans 3,3-dimethyl-2(2'-isobutyl-4'-methyll'-pentanyl)-cyclopropane carboxylic acid were dissolved under anatmosphere of nitrogen in 25 cc. of petroleum ether (boiling point=35-70C.) and then, 3.5 cc. of thionyl chloride were slowly added. Thesolution was agitated first for 1 hour and 30 minutes at roomtemperature, then for 30 minutes at 40 C. The reaction solution wasconcentrated to dryness under reduced pressure and then rectified toobtain 7.4 gm. of the desired dl-trans 3,3-dimethyl-2- 2'-isobutyl 4'methyl 1'-pentenyl)- cyclopropanecarboxylic acid chloride having aboiling point of 118 C. under 1.5 mm. pressure of mercury and arefractive index n =1.4775. The product was utilized as such for thenext step.

This product is not described in the literature.

Step E.Preparation of dl-trans 3,3-dimethyl-2-(2'-isobutyl 4' methyl 1'pentenyD-cyclopropanecarboxylate of dl-allethrolone:

Under an atmosphere of nitrogen, 7.335 gm. of dl-trans 3,3-dimethyl 2(2'-isobutyl-4-methyl 1'-pentenyl) cyclopropane carboxylic acid chloridewere introduced into 20 cc. of benzene and after a solution of 4 gm. ofdl-allet-hrolone in a mixture of 8 cc. of pyridine and 20 cc. of benzenewas added at 10 C., the reaction solution was agitated for 15 hours atroom temperature. Thereafter, first 1 cc. of formic acid and then waterwas added. The aqueous phase was extracted with ethyl ether and theether extracts were combined, successively washed with a dilute aqueoussolution of hydrochloric acid, with an aqueous solution of sodiumbicarbonate and finally with water, and then dried and concentrated todryness.

The resultant residue was dissolved in benzene and the benzene solutionwas passed through an alumina column,

Ultraviolet spectra (in ethanol) max.: 225 mu(e=20.300)

This product is not described in the literature.

EXAMPLE I-II Preparation of dl-trans 3,3 dimethyl-2-(2',-diphenylvinyl)-cyclopropanecarboxylic acid and its ester withdl-allethrolone Step A.-Preparation of (3,3 diphenyl-2-propenyl)-phenylsulfone:

15.5 gm. of sodium phenyl sulfinate and 1.5 gm. of sodium carbonate wereintroduced into 80 cc. of methanol. Then 25.6 gm. of1-bromo-3,3-diphenyl-2-propene were added to the reaction mixture underan atmosphere of nitrogen and at room temperature which was thenagitated for 1 hour and 30 minutes. Next, the reaction mixture waspoured into cold water and extracted with methylene chloride. Themethylene chloride extracts were combined, washed with water, dried andconcentrated to dryness. The residue was partly crystallized. Theprecipitate formed was isolated by vacuum filtering and dried to obtain25.48 gm. of (3,3-diphenyl-2-propenyl)-phenyl sulfone having a meltingpoint of 104 C. A sample of this product, recrystallized from isopropylether, had a melting point of 106 C. Analysis: C H SO molecularweight=334.43. Calculated (percent): C, 75.41;'*H, 5.42; S, 9.58. Found(percent): C, 75.3; H, 5.4; S, 9.4.

This product is not described in the literature.

Step. E.Preparation of ethyl dl-trans 3,3-dimethyl-2-(2',2-diphenylvinyl)cyclopropanecarboxylate:

Under an atmosphere of nitrogen, 21.6 gm. of potassium tertbutylatetitering 87% and 28.08 gm. of (3,3-diphenyl-Z-propenyl) phenyl sulfonewere introduced into 150 cc. of dimethylsulfoxide and the mixture wasagitated for minutes at 105 C. Then 17.5 cc. of ethylzap-dimethyl-acrylate were added and the reaction mixture was agitatedfor 2 hours, followed by addition of 17.5 cc. more of ethyl.8,fl-dimethylacrylate and the mixture was agitated for 7 hours at 105C. Thereafter the reaction mixture was cooled to 0 C. and acidified witha dilute aqueous solution of hydrochloric acid. the aqueous phase wasextracted with methylene chloride and the methylene chloride extractswere combined; washed first with an aqueous solution of sodiumbicarbonate, then with water, then dried and concentrated to dryness.The partly crystal- 'lized residue was filtered to eliminate anyimpurity. The filtrate was subjected to chromatography through aluminawith elution with cyclohexane to obtain the desired ethyl dl-traus 3,3dimethyl-Z-(2',2'-diphenylvinyl)-cyclopropanecarboxylate which was usedas such for the next step.

This product is not described in the literature.

Step C.-Preparation of dl-trans 3,3-dimethyl-2-(2',2'-diphenylvinyl)-cyclopropanecarboxylic acid:

42.7 cc. of a 2 N methanolic sodium hydroxide solution were introducedinto 100 cc. of methanol and 10 cc. of water, followed by 18.45 gm. ofethyl dl-trans 3,3- dimethyl 2(2',2'-diphenylvinyl)-cyclopropanecarboxylate were added thereto. Themixture was brought to reflux and maintained there for 1 hour and 30minutes. The methanol was removed by distillation and water was added.Next the aqueous phase was extracted with ethyl ether to eliminate theneutral fraction and the combined ether extracts were washed with waterand the wash water was combined with the principal aqueous phase. Thenthe entire aqueous phase was acidified with a dilute aqueous solution ofhydrochloric acid which was then repeatedly extracted with methylenechloride; the methylene chloride solutions were combined, washed withwater, dried and concentrated to dryness to obtain 7.95 gm. of (ll-trans3,3 dimethyl-2-(2,2' diphenylvinyl)-cyclopropanecarboxylic acid having amelting point of 115 C. A sample of this product crystallized from amixture of isopropyl ether and petroleum ether, had a melting point of115 C. Analysis: C H O molecular weight: 292.36. Calculated (percent):C, 82.15; H, 6.89. Found (percent): C, 82.1; H, 7.0.

According to its N.M.R. spectra, this product consisted of the transderivative containing about 10% of the cis derivative. This product isnot described in the literature.

Step D.-Preparation 0f dl-trans 3,3-dimethyl-2-(2',2'- diphenylvinyl)cyclopropanecarboxylic acid chlorides:

2.5 gm. of dl-trans 3,3-dimethyl-2-(2',2'-diphenylvinyl)-cyclopropanecarboxylic acid were introduced into 10 cc. of benzene andafter the addition of 0.9 cc. of thionyl chloride, the mixture wasmaintained at room temperature for 20 minutes, then heated to C. andmaintained at this temperature for 3 hours. Excess benzene and thionylchloride were eliminated by distillation under vacuum. The raw-dl-trans3,3-dimethyl-2-(2', '-diphenylvinyl)-cyclopropanecarboxylic acidchloride thus obtained in a quantitative yield was utilized as such forthe next step.

This product is not described in the literature.

Step E.Preparation of dl-trans 3,3-dimethyl-2-(2,2'-diphenylvinyl)-cyclopropanecarboxylate of dl-allethrolone:

The raw dl-trans 3,3-dimethyl-2-(2', '-diphenylvinyl)-cyclopropanecarboxylic acid chloride (corresponding to 2.5 gm. of acid)was introduced into 13 cc. of benzene and 1-.2 cc. of pyridine and 1.3gm. of dl-allethrolone were added thereto. The reaction mixture wasagitated for about 15 hours at room temperature. The precipitate formedwas eliminated by filtration and the benzene filtrate was washed firstwith a dilute aqueous solution of hydrochloric acid, then with water,then with an aqueous solution of sodium bicarbonate and lastly againwith water. Next the benzene solution was dried and concentrated todryness. The residue was subjected to chromatography through aluminawith elution with benzene to obtain 2.034 gm. of dl-trans3,3-dimethyl-2-(2, '-diphenylvinyl)-cyclopropanecarboxylate ofdl-allethrolone having a refractive index n =1.569. Analysis: C H Omolecular weight=426.53. Calculated (percent): C, 81.66; H, 7.09. Found(percent): C, 81.9; H, 7.2.

Ultraviolet spectra (in ethanol) A max.: 227 m (e=28,100)

7\ max.: 262 m (e=17,050)

This product is not described in the literature.

EXAMPLE IV Preparation of dl-trans3,3-dimethyl-Z-cyclopentylidenemethyl-cyclopropanecarboxylic acid andits ester with dl-allethrolone Step A.-Preparation of(2-cyclopentylidene-ethyl)- 17 sium hydroxide to obtain 15 gm. of(2-cyclopentylideneethyl)-phenyl sulfone having a melting point .of 68C. A sample of the product crystallized from isopropyl ether had amelting point of 68 C. Analysis: 11 80 molecular Weight=236.33.Calculated (percent): C, 66.06; H, 6.82; S, 13.57. Found (percent): C,65.8; H, 6.8; S, 13.2.

This product is not described in the literature.

The l-bromo 2-cyclopentylidene-ethane was prepared according to theprocess described in Bull. Soc. Chim., 1964, p. 2618.

Step B.Preparation of ethyl dl-trans 3,3-dimethyl-2-cyclopentylidene-methyl-cyclopropanecarboxylatez Under an atmosphere ofnitrogen, first 16.5 gm. of potassium tert.-butylate titering 87% then15 gm. of (2- cyclopentylidene-ethyl)phenyl sulfone were introduced into100 cc. of dimethylformamide. The mixture was agitated for 10 minutesand then 16 cc. of ethyl 5,,8-dimethylacrylate were added over about 10minutes and the reaction mixture was agitated for 3 hours. Thereafter,the reaction mixture was cooled to 0 C. and poured into a dilute aqueoussolution of hydrochloric acid. The aqueous phase was extracted withmethylene chloride, the methylene chloride extracts were combined,washed first with a dilute aqueous solution of sodium bicarbonate, thenwith water, then dried and concentrated to dryness under reducedpressure. The resultant residue was rectified under reduced pressure toobtain 12.28 gm. of raw ethyl dl-trans 3,3dimethyl-2-cyclopentylidene-methylcyclopropanecarboxylate having aboiling point of 88 C. under 0.05 mm. pressure of mercury, and it wasutilized as such for the following step.

This product is not described in the literature.

Step C.Preparation of dl-trans3,3-dimethyl-2-cyclopentylidene-methyl-cyclopropanecarboxylic acid:

Under an atmosphere of nitrogen, 12.28 gm. of raw ethyl dl-trans 3,3dimethyl 2-cyclopentylidene-methylcyclopropanecarboxylate wereintroduced into a mixture consisting of 32 cc. of a 2 N methanolicsodium hydroxide solution, 5 cc. of water and 5 cc. of methanol. Thereaction mixture was refluxed for 1 hour and 30 minutes, then cooled toroom temperature and a waterice mixture was added. Next, the aqueousphase was extracted with ethyl ether to eliminate the neutral fractionsand the combined ether extracts were washed with water. The aqueous washwaters were combined with the principal aqueous phase which was thenacidified with a dilute aqueous solution of hydrochloric acid. Then theacidified aqueous phase was extracted with methylene chloride and themethylene chloride extracts were combined, Washed with water, dried andconcentrated to dryness under reduced pressure. The residue wasrectified under vacuum to obtain 5.27 gm. of dl-trans 3,3-dimethyl- 2cyclopentylidene-methyl cyclopropanecarboxylic acid having a boilingpoint of 115 C. under 0.1 mm. pressure of mercury and a melting point of59 C. Analysis: C H O molecular weight: 194.26. Calculated (percent): C,74.19; H, 9.34. Found (percent): C, 74.1; H, 9.3.

This product is not described in the literature.

Step D.Preparation of dl-trans 3,3-dimethyl-2-cyclopentylidene methylcyclopropanecarboxylic acid chloride:

Under an atmosphere of nitrogen, 2.5 gm. of dl-trans 3,3 dimethyl2-cyclopentylidene-methyl-cyclopropanecarboxylic acid were introducedinto cc. of benzene and 1.04 cc. of thionyl chloride were added withinabout 30 minutes and under agitation and the reaction mixture wasagitated for 1 hour at room temperature. The excess benzene and thionylchloride were eliminated by distillation and the residue was rectifiedunder reduced pressure to obtain 2.2 gm. of raw dl-trans3,3-dimethyl-2-cyclopentylidene-methyLcyclopropanecarboxylic acidchloride having a boiling point of 82" C. under 025 mm. pressure ofmercury and it was utilized as such for the next step.

This product is not described in the literature.

Step E.Preparation of dl-trans 3,3-dimethyl-2-cyclopentylidene methylcyclopropaneearboxylate of dl-allethrolone:

Under an atmosphere of nitrogen, 2.2 gm. of dl-trans 3,3 dimethyl2-cyclopentylidene-methyl-cyclopropanecarboxylic acid chloride and 2 cc.of pyridine were introduced into 15 cc. of anhydrous benzene. 1.75 gm.of dl-allethrolone dissolved in 5 cc. of benzene were added over about10 minutes and the mixture was agitated for about 15 hours at roomtemperature. The precipitate formed was eliminated by filtration and thebenzene filtrate was washed first with saltwater, then with a diluteaqueous solution of hydrochloric acid and again with salt water. Theaqueous phases were extracted with sulfuric ether and the ether extractswere combined with the henzene solution. The organic solution thusobtained was dried and concentrated to dryness. The residue wassubjected to chromatography through an alumina column with elution withbenzene and methylene chloride to ob tain 3.015 gm. of dl-trans3,3-dimethyl-2-cyclopentylidenemethyl-cyclopropanecarboxylate ofdl-allethrolone having a refractive index n =1.5195.

Ultraviolet spectra (in ethanol) rmax; 225-236 mp.(e=20,700)

Analysis: C H 0 molecular weight=328.43. Calculated (percent): C, 76.79;H, 8.59. Found (percent): C, 76.6; H, 8.4.

This product is not described in the literature.

EXAMPLE V Preparation of dl-trans 3,3dimethyl-Z-cyclohexylidenemethyl-cyclopropanecarboxylic acid and itsester with dl-allethrolone Step A.Preparation of (2-cyclohexylidene-ethyl)- phenyl sulfone:

First, 38.5 gm. of sodium phenyl sulfinate and then 3.85 gm. of sodiumcarbonate were introduced into 116 cc. of methanol and 44 gm. of freshlyprepared l-bromo- 2-cyclohexylidene-ethane were added dropwise over 30minutes and at room temperature. The reaction mixture was then agitatedfor 1 hour and 30 minutes at room temperature after which the reactionmixture was poured into 400 cc. of ice water. The precipitate formed wasvacuum filtered, washed with water and dried. The raw product thusobtained was dissolved at high temperature in a mixture consisting ofmethylene chloride and methanol. The solution obtained was dried overmagnesium sulfate, concentrated to a small volume and admixed withisopropyl ether. The precipitate formed was vacuum filtered and dried toobtain 36.4 gm. of (2-cyclohexylidene-ethyl)-phenyl sulfone, having amelting point of 70 C. A sample of this product, crystallized fromisopropyl ether, had a melting point of 70 C. Analysis: C I-1 molecularweight=250.35. Calculated (percent): C, 67.16; H, 7.24; S, 12.81. Found(percent): C, 67; H, 7.1; S, 12.5.

This product is not described in the literature.

The 1 -brorno-Z-cyclohexylidene-ethane was prepared according to theprocess described in Helv. (1942), vol. 25, p. 29.

Step B.Preparation of ethyl dl-trans 3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylate:

20.6 gm. of potassium tert.-hutylate titering 87% were introduced intocc. of dimethylformamide and then 20 gm. of(2-cyclohexylidene-ethyl)-phenyl sulfone were added thereto. After 10minutes, 17.3 cc. of ethyl 13,13- dimethylacylate were added and themixture was agitated for 1 hour at room temperature. Thereafter, thereaction mixture was cooled to about +5 C., acidified with a diluteaqueous solution of hydrochloric acid and the aqueous phase wasextracted with methylene chloride.

The methylene chloride solution obtained was washed first with anaqueous solution of sodium bicarbonate,

then with water, dried over magnesium sulfate and concentrated todryness under reduced pressure to obtain 22.75 gm. of ethyl dl-trans3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylic which wasutilized as such for the next step.

This product is not described in the literature.

Step C.Preparation of dl-trans3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylic acid:

22.75 gm. of ethyl dl-trans 3,3-dimethyl-2-cyclohexylidene methylcyclopropanecarboxylate were introduced into a mixture consisting of 70cc. of a 2 N methanolic sodium hydroxide solution, 2.5 cc. of water and25 cc. of methanol. The reaction mixture was heated to reflux andmaintained at reflux for 45 minutes. Thereafter, the methanol wasremoved under reduced pressure and water was added to the residue. Theinsoluble matter formed (the sodium salt of the desired acid) was vacuumfiltered, then washed first with water, then with ether, and thesewash-waters were eliminated. The said product was agitated with 100 cc.of a dilute aqueous solution of hydrochloric acid and 100 cc. ofmethylene chloride until total dissolution had been attained. Theorganic phase was then separated by decanting and it was washed withwater. The wash waters were extracted with methylene chloride. The saidmethylene chloride extracts were combined with the principal methylenechloride solution, dried over magnesium sulfate and finally concentratedto dryness under reduced pressure. The residue thus obtained was admixedwith petroleum ether and the precipitate formed was vacuum filtered,washed with petroleum ether and dried to obtain the desired dl-trans3,3- dimethyl-2-cyclohexylidene-methyl-cyclopropane carboxylic acid,having a melting point of 88 -89 C. Analysis: c,,n,,o,; molecularweight=208.29. Calculated: (percent): C, 74.96; H, 9.67. Found(percent): C, 75.1; H, 9.4.

This product is not described in the literature.

Step D.Preparation of dl-trans 3,3-dimethyl-2cyclohexylidene-methyl-cyclopropanecarboxylic acid chloride:

3 gm. of dl-trans3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylic acid wereintroduced into 15 cc. of petroleum ether (boiling point=5070 C.) andthen 1.55 cc. of thionyl chloride were added over about 30 minutes, andthe mixture was agitated at room temperature for about 1 hour.Thereafter, the petroleum ether was eliminated under reduced pressureand the raw acid chloride was rectified under reduced pressure to obtain2.66 gm. of the desired dl-trans3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylic acidchloride having a boiling point of 88-90 C. under 0.35 mm. pressure ofmercury and was utilized as such for the next step. This productoccurred in liquid form at room temperature.

This compound is not described in the literature.

Step E.Preparation of dl-trans3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylate ofdl-allethrolone:

1.56 gm. of dl-trans3,3-dimethyl-2-cyclohexylidenemethyl-cyclopropanecarboxylic acidchloride were introduced into a mixture of 15 cc. of benzene and 1.9 cc.of pyridine. Then a solution of 1.050 gm. of dl-allethrolone in 5 cc. ofbenzene was added dropwise within a few minutes and the mixture wasagitated for about 15 hours at room temperature. Thereafter, theprecipitate formed was vacuum filtered and the resultant filtrate waswashed successively with a dilute aqueous solution of hydrochloric acid,with an aqueous solution of sodium chloride, with an aqueous solution ofsodium bicarbonate and finally again with an aqueous solution of sodiumchloride. The aqueous wash waters were combined and extracted withbenzene. The benzene extract was combined with the principal benzenesolution and the entire benzene solution was then dried over magnesiumsulfate and concentrated to dryness under reduced pressure. Therecovered residue was purified by chromatography through alumina withelution with cyclohexane to obtain 1.500 gm. of dl-trans3,3-dimethyl-2-cyclohexylidene methyl-cyclopropanecarboxylate ofdl-allethrolone having a refractive index n =1.5l5. Analysis: C H Omolecular weight: 342.46. Calculated (percent): C, 77.15; H, 8.82. Found(percent): C, 77.4; H, 9.0.

Ultraviolet spectra (in ethanol) A max.: 223 mp. (e=19,500)

This product is not described in the literature.

EXAMPLE VI Preparation of dl-trans3,3-dimethyl-2-(2-propyl-1-pentenyl)-cyclopropanecarboxylic acid and itsdl-allethrolone ester Using the procedure of Example I,l-bromo-3-propyl- 2-hexene was reacted with sodium phenyl sulfinate toform (3-propyl-2-hexenyl)-phenyl sulfone which was then reacted withethyl 18,}9-dimethyl-acrylate to form ethyl dltrans3,3-dimethyl-2-(2'-propyl 1' pentenyl)-cyclopropanecarboxylate having aboiling point of 80 C. at 0.06 mm. Hg and a refractive index n =1.464.The said ethyl ester was hydrolyzed under alkaline conditions to formdl-trans 3,3-dimethyl-2-(2'-propyl- '-pentenyl)-cyclopropane carboxylicacid having a boiling point of 116 C. at 0.05 mm. Hg and a refractiveindex n =1.4755 which was then reacted with thionyl chloride to obtaindl-trans 3,3-dimethyl-2-(2'-propyl- '-pentenyl)-cyclopropanecarboxylicacid chloride having a boiling point of C. at 0.04 mm. Hg and arefractive index n 1.4795.

The said acid chloride was then reacted with dl-allethrolone to formdl-trans 3,3 dimethyl-2-(2-propyl-1'- pentenyl)-cyclopropanecarboxylateof dl-allethrolone having a refractive index n =1.499.

EXAMPLE VII Preparation of dl-trans 3,3-dimethyl-2-(2'-isopropyl-3'methyl- -butenyl)-cyclopropanecarboxylic acid and its dl-allethroloneester Using the procedure of Example I,1-bromo-3-isopropyl-4-methyl-2-pentene was reacted with sodium phenylsulfinate to form (3-isopropyl-4-methyl-2-pentenyl)-phenyl sulfonehaving a melting point of 50 C. which was then reacted with ethyl,13,fl-dimethylacrylate to form ethyl dl-trans 3,3dimethyl-Z-(2'-isopropyl-3'-methyl-l'- butenyl) cyclopropanecarboxylate.The said ethyl ester was hydroylzed under alkaline conditions to formdltrans 3,3 dimethyl-Z-(2'-isopropyl-3'-methyl-l'-butenyl)- cyclopropanecarboxylic .acid having a melting point of 135 C. which was then reactedwith thionyl chloride t form dl-trans 3,3 dimethyl-2-(2'-isopropyl-'-methyl-1'- butenyl)-cyclopropanecarboxylic acid chloride having aboiling point of 78 to 80 C. at 0.1 mm. Hg.

The said acid chloride was then reacted with dl-allethrolone to formdl-trans 3,3-dimethyl-2-(2'-isopropyl-3- methyl- '-butenyl)cyclopropanecarboxylate of dl-allethrolone having a refractive index n1.497.

EXAMPLE VIII Preparation of dl-trans 3,3dimethyl-2-(26'dimethylcyclopropanecarboxylic acid and itsdl-allethrolone ester Using the procedure of Example I,l-bromo-2-(2',6'- dimethyl-cyclohexylidene)-ethane was reacted withsodium phenyl sulfinates to form[2-(2',6'-dimethylcyclohexylidene)-ethyl]-phenyl sulfone having amelting point of 96 C. which was then reacted with ethyl3,5-dimethylacrylate to form ethyl dl-trans 3,3-dimethyl-2-(2',6'-dimethyl cyclohexylidene-methyl) cyclopropanecarboxylate having a boilingpoint of l05110 C. at 0.5 mm. Hg. The said ethyl ester was thenhydrolyzed under alkaline conditions to form dl-trans3,3-('EmethyB-2-(2',6'- dirnethyl-cyclohexylidene-methyl)cycliupropanecambox- The said acid chloride was then reacted with d1-allethrolone to form dl-trans3,3-dimethyl-2-(2',6'-dimethyl-cyclohexylidene-methyl)-cyclopropanecarboxylate of dl-alletbrolone having a refractive index n =1.5136.

EXAMPLE IX Preparation of dl-trans 3,3 dimethyl-2-(4', '-dimethy1-cyclohexylidene-methyl) cyclopropanecarboxylic acid and itsdl-allethrolone ester Using the procedure of Example I,1-hromo-2-(4',4'-dimethyl-cyclohexylidene)-ethane was reacted withsodium phenyl sulfinate to form[2-(4',4'-dimethyl-cyclohexylidene)-ethyl]-phenyl sulfone having amelting point of 110 C. which was then reacted with methyl{LB-dimethylacrylate to form methyl dl-trans 3,3-dimethyl-2-(4',4'-dimethyl cyclohexylidene-methyl) cyclopropanecarboxylate having aboiling point of 120 C. at 1 mm. Hg. The said methyl ester washydrolyzed under alkaline conditions to form dl-trans3,3-dimethy1-2-(4,4-dimethyl-cyclohexylidene-methyl)-cyclopropanecarhoxylic acid having a melting point of 96 C. which was then reactedwith thionyl chloride to form dl-trans3,3-dimethyl-2-(4,4'-dimethyl-cyclohexylidene-methyl)-cyclopropanecarboxylic acid chloride having a boiling point of 115 C. at 0.7 mm. Hgand a refractive index n 1.5005.

The said acid chloride was then reacted with dl-allethrolone to formdl-trans 3,3-dimethyl2-(4,4-dimethyl-cyclohexylidene-methyl)cyclopropanecarboxylate of dl-allethrolone having a refractive index n1.5110.

EXAMPLE X Preparation of dl-trans 3,3 dimethyl-2-(3',3',5,'-tetramethyl-cyclohexylidene-methyl)-cyclopropane carboxylic acid andits dl-allethrolone ester Using the procedure of Example I,1-bromo-2-(3',3',5', 5'-tetramethyl-cyclohexylidene)-ethane was reactedwith sodium phenyl sulfinate to form[2-(3',3',5,5-tetramethyl-cyclohexylidene)-ethyl]-phenyl sulfone havinga melting point of 55 C. which was then reacted with ethyl3,3-dimethylacrylate to form ethyl dl-trans 3,3-dimethyl-2-(3,3',S',5-tetramethyl cyclohexylidene methyl) cyclopropanecarboxylate. The said ethyl ester was then hydrolyzed under alkalineconditions to form dl-trans 3,3- dimethyl 2 (3,3',5', '-tetramethylcyclohexylidenemethyl) cyclopropanecarboxylic acid having a meltingpoint of 116 C. which was then reacted with thionyl chloride to formdl-trans 3,3-dimethyl-2-(3',3',5',5'-tetramethylcyclohexylidene-rnethyl) cyclopropanecarboxylic acid chloride having aboiling point of 119 C. at 0.8 mm. Hg and a refractive index n =1.499.

The said acid chloride was then reacted with dl-allethrolone to formdl-trans 3,3-dimethyl-2-(3',3',5,5-tetramethyl-cyclohexylidene methyl)cyclopropanecarboxylate of dl-allethrolone.

EXAMPLE XI Preparation of dl-trans3,3-dimethyl-2-(2',3',5',6'-tetrahydro 4pyranylidene-methyl)-cyclopropanecarboxylic acid and its dl-allethroloneester Using the procedure of Example I, l-bromo-2-(2,3',5,-6'-tetrahydro-4-pyranylidene)-ethane was reacted with sodium phenylsulfinate to form [2-(2',3',5',6'-tetrahydro-4'-pyranylidene)ethyl]-phenyl sulfone having a melting point of 68 C.which was then reacted with ethyl flfl-dimethylacrylate to form ethyldl-trans 3,3-dimethyl-2-(2,- 3',5,6'-tetrahydro 4'pyranylidene-methyl)-cyclopropane carboxylate. The said ethyl ester wasthen hydrolyzed under alkaline conditions to form dl-tran3,3-dimethyl-2-(2,3',5,6'-tetrahydro 4' pyranylidene-methyl)-cyclopropanecarboxylic acid having a melting point of l02103 C.which was then reacted with thionyl chloride to form dl-trans3,3-dimethyl-2-(2',3',5,6-tetrahydro 4'pyranylidene-methyl)-cyclopropanecarboxylic acid chloride having aboiling point of 82 C. at 0.1 mm. Hg.

The acid chloride was then reacted with dl-allethrolone to form dl-trans3,3-dimethyl-2-(2,3',5',6'-tetrahydro-4'-pyranylidene-methyl)-cyclopropanecarboxylate of dl-allethrolone having arefractive index n =1.520.

EXAMPLE XII Preparation of3-phenyl-2-(1'-isobutenyl)-cyclopropanecarboxylic acid and itsdl-allethrolone ester Using the procedure of Example I(3-methyl-2-butenyl) -phenyl sulfone produced as in French Pat. No.1,483,- 715 was reacted with ethyl cinnamate to form ethyl 3-phenyl-2-(1' isobutenyl)-cyclopropanecarboxylate which was hydrolyzedunder alkaline conditions to form 3- phenyl 2(1'-isobutenyl)-cyclopropanecarboxylic acid having a melting point of104 C.

The said acid was reacted with thionyl chloride to form 3phenyl-2-(1'-isobutenyl)-cyclopropanecarboxylic acid chloride having aboiling point of 101 to 103 C. at 0.3 mm. Hg and a refractive index n=1.5522 which was then reacted with dl-allethrolone to form 3-phenyl2-(1-isobuteny1)-cyclopropanecarboxylate of dl-allethrolone having arefractive index n =1.5487.

EXAMPLE XDI Preparation of3-methyl-2-(1-isobutenyl)-cyclopropanecarboxylic acid and itsdl-allethrolone ester Using the procedure of Example I (3-methyl-2-butenyl)-phenyl sulfone produced as in French Pat. No. 1,483,- 715 wasreacted with ethyl crotonate to form ethyl 3- methyl-2-( 1'-isobuteny1)cyclopropanecarboxylate having a boiling point of 52 C. at 0.2 mm. Hgand a refractive index n =1.462 which was hydrolyzed under alkalineconditions to form 3-methyl-2-(1-isobutenyl)-cyclopropanecarboxylic acidhaving a boiling point of 81-82 C. at 0.07 mm. Hg and a refractive indexn 5=1.4820.

The said acid was reacted with thionyl chloride to form 3methy1-2-(1-isobutenyl)-cyclopropanecarboxylic acid chloride having aboiling point of 51 C. at 0.8 mm. Hg which was then reacted withdl-allethrolone to form 3-methyl-2-(1'-is0butenyl)-cyclopropanecarboxylate of dlallethrolonehaving a boiling point of 127 C. at 0.01 mm. Hg.

EXAMPLE XIV Preparation of3,3-dipropyl-2-(l'-isobutenyl)-cyclopropanecarboxylic acid and itsdl-allethrolone ester Using the procedure of Example I(3-methyl-2-butenyl)-phenyl sulfone produced as in French Pat. No.1,483,- 715 was reacted with ethyl 18,;3-dipropylacrylate to form ethyl3,3-dipropyl 2 (1-isobutenyl)-cyclopropanecarboxylate having a boilingpoint of 90-92 C. at 0.5 mm. Hg and a refractive index n =1.4660 whichwas hydrolyzed under alkaline conditions to form 3,3dipropyl-2-(1'-isobutenyl)-cyclopropanecarboxylic acid having a boiling point of116 C. at 0.1 mm. Hg and a refractive index n =1.4760.

The said acid was reacted with thionyl chloride to form 3,3 dipropyl 2l'-isobutenyl)-cyclopropanecarboxylic acid chloride having a boilingpoint of -85 C. at 0.1 mm. Hg and a refractive index n =l.4819 which wasreacted with dl-allethrolone to form 3,3-dipropyl-2-(1'-isobutenyl)-cyclopropanecarboxylate of dl-allethrolone.

23 EXAMPLE XV Preparation of 2-(l'-isobutenyl)-spiro-[2,5]-octane-1-carboxylic acid and its dl-allethrolone ester Using the procedure ofExample I (3-methyl-2-butenyl)-phenyl sulfone produced as in French Pat.No. 1,483,- 715 was reacted with ethyl cyclohexylideneacetate to formethyl 2-(1'-isobutenyl)-spiro-[2,5]-octane-l-carboxylate having aboiling point of 9397 C. at 0.7 mm. Hg which was hydrolyzed underalkaline conditions to form 2-(1'-isobutenyl)-spiro [2,5]octane-l-carboxylic acid having a melting point of 80 C.

The said acid was reacted with thionyl chloride to form2-(l-isobutenyl-spiro [2,5] octane-l-carboxylic acid chloride having aboiling point of 7880 C. at 0.2 mm. Hg and a refractive index n =1.5080which was reacted with dl-allethrolone to form 2-( l'-isobutenyl)-spiro-[2,51-octane-1-carboxylate of dl-allethrolone having a refractive indexn =5l93.

EXAMPLE XVI Preparation of 2-(1-isobutenyl)-spiro-[2,4]-heptane-1-carboxylic acid and its dl-allethrolone ester Using the procedure ofExample XV (3-methyl-2-butenyl)-phenyl sulfone was reacted with ethylcyclopentylideneacetate to form ethyl 2-(1'-isobutenyl)-spiro[2,4]-heptane-l-carboxylate which was hydrolyzed under alkaline conditions toform 2-(1'-isobutenyl)-spiro-[2,4]-heptane-l-carboxylic acid.

The said acid was then reacted with thionyl chloride to form2-(1'-isobutenyl) spiro [2,4]-heptane-1-carboxylic acid chloride whichwas then reacted with dl-allethrolone to form2-(1'-isobutenyl)-spiro-[2,4]-heptane-1-carboxylate of dl-allethrolone.

EXAMPLE XVII Preparation of dI-trans3,3-dimethyl-2-cyclopentylidenemethyl-cyclopropanecarboxylate ofcis-cinerolone ester Using the procedure of Example I, 1.15 gm. ofdltrans 3,3-dimethyl-2-cyclopentylidenemethylcyclopropanecarboxylic acidchloride produced in Step D of Example IV was reacted with 0.9 gm. ofcis-cinerolone to form 1.24 gm. of dl-trans3,3-dimethyl-2-cyclopentylidene-methylcyclopropanecarboxylate ofcis-cinerolone having a refractive index :1 :1.5179.

EXAMPLE XVIII Preparation of dl-trans 3,3-dimethyl-Z-cyclopentylidenemethyl-cyclopropanecarboxylate of 1-oxo-3-methyl-2-(2'-cyclohexenyl)-2-cyclopentene-4-ol Using the procedure of Example Idl-trans 3,3-dimethyl 2 cyclopentylidenemethyl cyclopropanecarboxylicacid chloride produced as in Step D of Example IV was reacted with1-oxo-3-methyl-2-(2'-cyclohexenyl)- 2-cyclopentene-4-ol (Coll. Czech.,vol. 25, 1960, p. 1835) to form dl-trans3,3-dimethyl-2-cyclopentylidenemethylcyclopropanecarboxylate of1-oxo-3-methyl-2-(2'-cyclohexenyl)-2-cyclopentene-4-ol having arefractive index of n =1.523.

- EXAMPLE XIX Preparation of dl-trans3,3-dimethyl-2-cyclobutylidenemethyl-cyclopropanecarboxylate ofdl-allethrolone Using the procedure of Example I,l-bromo-Z-cyclobutylidene-ethane was reacted with sodium phenylsulfinate to form (2-cyclobutylidene-ethyl)-phenyl sulfone having amelting point of 76 to 78 C. which was then reacted with ethyl13,;8-dimethylacrylate to form ethyl dl trans3,3dimethyl-Z-cyclobutylidenemethyl-cyclopropanecarboxylate. The saidethyl ester was hydrolyzed under alkaline conditions to form dl-trans3,3-dimethyl-2-cyclobutylidenemethyl-cyclopropanecarboxylic acid.

The said acid was reacted with thionyl chloride to form dl-trans 3,3dimethyl 2-cyclobutylidenemthyl-cyclopro- 24 panecarboxylic acidchloride which was then reacted with dl-allethrolone to form dl-trans3,3-dimethyl-2-cyclobutylidene-methyl-cyclopropanecarboxylate ofdl-allethrolone. The compounds obtained at the different steps of theExamples VI to XIX are not described in the literature.

EXAMPLE XX Preparation of dl-cis and trans 2,2,5-trimethyl-spiro-[2,5]-

4-octene-l-carboxylic acids and the trans acid ester withdl-allethrolone.

Step A.Preparation of (3-methyl-2-cyclohexenyl)- phenyl sulfone:

34.2 gm. of raw 3-methyl-2-cyclohexene-1-ol were introduced into 400 cc.of formic acid and then 68 gm. of sodium phenyl sulfinate were addedthereto. The mixture was agitated for 15 hours at room temperature andthen was poured into an water-ice mixture. Next. the reaction mixturewas extracted with methylene chloride and the methylene chlorideextracts were combined, washed first with water, then with an equeoussolution of sodium bicarbonate and again with water, then dried andconcentrated to dryness. The residue was admixed with a mixture ofisopropyl ether and petroleum ether and the resultant precipitate wasisolated by filtration, washed and dried to obtain 47 gm. of(3-methyl-2-cyclohexenyl)- phenyl sulfone. A sample of this product waspurified by dissolution in methylene chloride, concentration thereof andan addition of isopropyl ether to obtain the said sulfone having amelting point of 70 C. Analysis: C H O S; molecular weight=236.33.Calculated (percent): C, 66.06; H, 6.82; S, 13.57. Found (percent): C,66.3; H, 6.8; S, 13.3.

This product is not described in the literature.

Step B.-Preparation of ethyl dl-cis and trans2,2,5-trimethyl-spiro-[2,5]-4-octene-1-carboxylate:

(a) First, 9.5 gm. of potassium tert.-butylate, then 10 gm. of(3-methyl-2-cyclohexenyl)-phenyl sulfone were introduced into 50 cc. ofdimethylsulfoxide containing 1.5% of water, 9.5 cc. of ethylBfl-dimethylacrylate were added over about 5 minutes and the mixture wasagitated for 1 hour at room temperature. Then the reaction mixture wascooled to 0 and acidified with a dilute aqueous solution of hydrochloricacid. The aqueous phase was extracted with methylene chloride and themethylene chloride extracts were combined. The organic solution obtainedwas washed first with an aqueous solution of sodium bicarbonate, thenwith water, dried and concentrated to dryness under pressure to obtain8.8 gm. of substantially pure ethyl di-trans 2,2,5-trimethyl-spiro-[2,5]4octene-1- carboxylate.

This product is not described in the literature.

(b) The same method as described above was repeated butdimethylsulfoxide containing 1.5% of water was replaced withdimethylsulfoxide containing 0.08% of water to obtain substantially pureethyl dl-cis 2,2,5-trimcthylspiro-[2,51-4-octene-1-carboxylate.

This product is not described in the literature.

Step C.(a)Preparation of dl-trans 2,2,5-trimethylspiro-[2,5]-4-octene-1-carboxylic acid:

1 cc. of water and 8.8 gm. of ethyl dl-trans2,2,5-trimethyl-spiro-[2,5]-4-octene 1 carboxylate were introduced intoa mixture of 20 cc. of methanol and 30 cc. of a 2 N methanolic sodiumhydroxide solution under an atmosphere of nitrogen. The mixture wasbrought to reflux and maintained at reflux for 1 hour. Then the methanolwas eliminated by distillation and the remainder was diluted with water.The aqueous phase was extracted with ethyl ether and the ether extractswere combined and washed with water. The ether solution, which contained an undesired neutral fraction, was eliminated. All of the aqueousphases were acidified with a dilute aqueous solution of hydrochloricacid and then were extracted with methylene chloride. The methylenechloride extracts were combined, washed with an aqueous solution ofsodium chloride, dried and concentrated to, dryness. The residue wasadmixed with isopropyl ether and the precipitate formed was isolated byvacuum filtering and dried to obtain the desired dl-trans2,2,5-trimethyl-spiro-[2,5]-4 octene-l-carboxylic acid having a doublemelting point: 122 C., then 130132 C. Analysis: C H O molecular weight:194.26. Calculated (percent): C, 74.19; H, 9.33. Found (percent): C,74.4; H, 9.3.

The R.M.N. spectra of this product showed an ethylenic proton at 288 Hz.which is characteristic of the trans isomer. This product is notdescribed in the literature.

(b) Preparation of dl-cis 2,2,5-trimethyl-spiro-[2,5]-4-octene-1-carboxylic acid:

By starting with ethyl dl-cis 2,2,5-trimethyl-spiro- [2,5]-4-octene-1-carboxylate and using the same procedure as described for thepreparation of trans acid, the dl-cis 2,2,5-trimethyl-spiro-[2,5] 4octene-l carboxylic acid was obtained having a melting point of 140-142C. after recrystallization from isopropyl ester. Analysis: G i-1molecular weight=194.26. Calculated (percent): C, 74.19; H, 9.33. Found(percent): C, 74.3; H, 9.4.

The R.M.N. spectra of this product showed an ethylenic proton at 322 Hz.which is characteristic of the cis isomer. This product is not describedin the literature.

Step D.Preparation of dl-trans 2,2,5-trimethyl-spiro-[2,5]-4-octene-1-carboxylic acid chloride:

2.5 gm. of dl-trans 2,2,5- trimethyl-spiro-[=2,5]-4octene-l-carboxylicacid were introduced into a mixture of 15 cc. of petroleum ether(boiling point=30-70 C.) and cc. of benzene. Next, 1.4 cc. of thionylchloride were added dropwise and the mixture was agitated for 1 hour atroom temperature and then at 60 C. for 20 minutes. Thereafter, 1.4 cc.of thionyl chloride were added, and the reaction mixture was agitatedfor 2 hours and 30 minutes at room temperature. The solvent and theexcess thionyl chloride were eliminated by distillation under vacuum.

The residue was rectified under vacuum to obtain 0.836 gm. of dl-trans2,2,5-trimethyl-spiro-[2,5]-4-octene-l-carboxylic acid chloride having aboiling point of 80 C. under 0.5 mm. pressure of mercury and it wasutilized as such for the next step.

This product is not described in the literature.

Step E.-Preparation of dl-trans 2,2,5-trimethyl-spiro-[2,5]-4-octene-l-carboxylate of dl-allethrolone:

1 cc. of pyridine and 0.836 gm. of dl-trans2,2,5-trimethyl-spiro-[2,5]-4-octene-1-carboxylic acid chloride wereintroduced into 5 cc. of benzene and then a solution of 0.600 gm. ofdl-allethrolone in 4 cc. of benzene was added dropwise. The mixture wasagitated for 16 hours at room temperature. Thereafter, the precipitateformed was eliminated by filtration and the benzene filtrate wassuccessively washed with a dilute aqueous solution of hydrochloric acid,with water, with an aqueous solution of sodium bicarbonate and againwith water. The solution was dried over magnesium sulfate andconcentrated to dryness. The residue was dissolved in cyclohexane andthe solution obtained was passed through an alumina column to obtain0.981 gm. of dl-trans 2,2,5-trimethyl-spiro-[2,5]-4-octene-l-carboxylate of dl-allethrolone. Analysis: C H Omolecular weight=328.43. Calculated (percent): C, 76.79; H, 8.59. Found(percent): C, 76.7; H, 8.3.

This product is not described in the literature.

EXAMPLE XXI Preparation of dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acid andits dl-allethrolone ester Step A.Preparation of dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropane carboxylic acid:

24 gm. of cyclopropyl triphenyl phosphonium bromide and 5 gm. of asuspension containing 50% of sodium hydride in Vaseline oil wereintroduced into 100 cc. of dimethoxyethane. The reaction mixture washeated to reflux and maintained at reflux for 15 minutes after which a26 mixture of 5.92 gm. of dl-trans caronaldehydic acid and 30 cc. ofdimethoxyethane were added dropwise. The reaction mixture was held atreflux for 1 hour and 30 minutes and then cooled. The insolublesubstance formed was eliminated by filtration and the filtrate wasconcentrated to dryness under reduced pressure. Water was added to theresidue and the insoluble matter formed was eliminated by filtration.This filtrate was acidified with a dilute solution of hydrochloric acidand the aqueous acid phase was extracted with ether. The ether extractswere combined, washed with an aqueous saturated solution of sodiumchloride, then dried, decolorized with animal charcoal and finallyconcentrated to dryness under reduced pressure to obtain a partiallycrystallized product. The crystals were separated from the oily portionby vacuum filtering over fritted glass. The product thus isolated wasrecrystallized from isopropyl ether to obtain 2.74 gm. of dl-trans 3,3dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acid having amelting point of C.

By starting with the filtrate and the mother liquors of isopropyl ethercrystallization and esterification with diazomethane, purification ofthe product obtained by chromatography and saponification gave a secondyield of 0.555 gm. of the same acid having a melting point of 84-85 C. Asample of this product after recrystallization from isopropyl ether hada melting point of C. Analysis: C H O molecular weight=l66.21.Calculated (percent): C, 72.26; H, 8.48. Found (percent): C, 72.0; H,8.5.

By ozonization of this compound in a chloroform media, followed bydecomposition of the ozonide in oxidizing media hydrogen peroxide, thetrans caronic acid was obtained (melting point=212 C.), whichestablished the trans structure of the starting cyclopropanecarboxylicacid. This structure was, furthermore, confirmed by the R.M.N. spectraof the compound which had a doublet at 96-1015 Hz. corresponding to theproton in the 1- position of the cyclopropane ring and of which thecoupling constant with the proton in the 2-position :5.5 Hz.)corresponded to a trans structure.

This dl-trans 3,3-dimethyl-Z-cyclopropylidenernethyl-1-cyclopropanecarboxylic acid is not described in the literature.

Step B.Preparation of dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acidchloride:

1.1 gm. of dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acid wereintroduced into 5 cc. of benzene and 0.55 cc. of thionyl chloride wereadded over about 15 minutes. Next, the reaction mixture was agitated for3 hours at room temperature, after which the solvent and the excessthionyl chloride were eliminated by distillation under reduced pressureto obtain 1.2 gm. of raw dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acidchloride. The product was utilized as such for the next step.

This compound is not described in the literature.

Step C.-Preparation of dl-trans 3,3-dimethyl-2-cyclopropylidenemethyl 1cyclopropanecarboxylate of diallethrolone:

First, 1.2 gm. of dl-trans 3,3-dimethyl-2-cyclopropylidenemethyl-l-transcyclopropanecarboxylie acid chloride, then 1.05 gm. of dl-allethrolonein solution in 8 cc. of benzene were introduced into a mixture of 5 cc.of henzene and 1.3 cc. of pyridine and the reaction mixture was agitatedfor 15 hours at room temperature. Then the precipitate formed waseliminated by filtration and the organic filtrate was washedsuccessively, with a dilute aqueous solution of hydrochloric acid, withan aqueous solution of sodium chloride, with an aqueous solution ofsodium bicarbonate and lastly again with an aqueous solution of sodiumchloride. After having been dried, the solution was concentrated todryness under reduced pressure. Then the residue was subjected tochromatography 27 through alumina to obtain 1.46 gm. of dl-trans3,3-dimethyl 2 cyclopropylidenemethyl 1 cyclopropanecarboxylate ofdl-allethrolone having a refractive index n =1.52l. Analysis: C H Omolecular weight=300.38. Calculated (percent): C, 75.97; H, 8.05. Found(percent): C, 75.8; H, 8.1.

Ultraviolet spectra (in ethanol) 'r max.: 223-224 mg. (e=18,200)

The R.M.N. spectra of this compound showed at 97.5

EXAMPLE XXII Preparation of dl-trans3,3-dimethyl-2-cyclobutylidenemethyl-l-cyclopropanecarboxylic acid andits dl-allethrolone ester Step A.--Preparation of dl-trans3,3-dimethyl-2-cyc1obutylidenemethyl-l-cyclopropanecarboxylic acid:

5.84 gm. of a 50% sodium hydride suspension in vaseline oil and 28.5 gm.of cyclobutyl triphenyl phosphonium bromide were introduced into 300 cc.of dimethoxyethane under an atmosphere of nitrogen. The reaction mixturewas brought to reflux and held at reflux for 40 minutes. Then a solutionof 6.8 gm. of dl-trans caronadelhydic acid in 25 cc. of dimethoxyethanewas added thereto over about 15 minutes. The reaction mixture was againheld at reflux for 30 minutes. The precipitate formed was eliminated byfiltration and the filtrate was concentrated to dryness. Water was addedto the residue and the precipitate formed was removed by filtration andwashed with water. The combined aqueous phases were extracted with etherand the aqueous solution was acidified with a dilute aqueous solution ofhydrochloric acid. The aqueous acid solution was extracted with etherand the acid ether extracts were combined, washed with water, dried andconcentrated to dryness. The residue was crystallized first fromisopropyl ether, then from ether to obtain 4.84 gm. of dl-trans3,3-dimethyl-2-cyclobutylidenemethyl-l-cyclopropanecarboxylic acidhaving a melting point of 98 C. Analysis: C H O molecular weight=180.24.Calculated (percent): C, 73.30; H, 8.95. Found (percent): C, 73.1; H,9.0.

The R.M.N. spectra of this compound showed at 82 87 Hz. a doublet whichcorresponded with the proton in the 1-position of the cyclopropane ring.The coupling constant of this proton and of the proton in the 2-position(-r= Hz.) had, therefore, a value characteristic of the trans formation.

This compound is not described in the literature.

Step B.Preparation of dl-trans3,3-dimethyl-2-cyclobutylidenemethyl-l-cyclopropanecarboxylic acidchloride:

Under an atmosphere of nitrogen, 2 gm. of dl-trans 3,3- dimethyl 2cyclobutylidenemethyl-cyclopropanecarboxylic acid were suspended in cc.of petroleum ether, (boiling point=50-70 C.) and then 1.2 cc. of thionylchloride were added to the reaction mixture which was then agitated for30 minutes at room temperature. The solvent and the excess thionylchloride were eliminated by distillation under vacuum and the residuewas rectified to obtain 1.88 gm. of dl-trans3,3-dimethyl-2-cyclobutylidene 1 cyclopropanecarboxylic acid chloridehaving a boiling point of 85 C. at 0.7 mm. Hg and a refractive index n=-l.5090. The product was utilized as such for the next step.

This compound is not described in the literature.

Step C.Preparation of dl-trans 3,3-dimethyl-2-cyclo- 28butylidenemethyl-l-cyclopropanecarboxylate of dl-allethrolone:

1.885 gm. of dl-trans3,3-dimethyl-2-cyclobutylidenemethyl-l-cyclopropanecarboxylic acidchloride were introduced into 5 cc. of benzene and then a solution of1.46 gm. of dl-allethrolone in a mixture of 2 cc. of pyridine and 10 cc.of benzene was added dropwise. Next, the reaction mixture was agitatedfor 15 hours at room temperature and a few drops of formic acid wereadded thereto and the reaction mixture was then diluted with water. Theorganic phase was separated by decanting and the aqueous phase wasextracted with ether. The ether extracts were combined with theprincipal organic phase and the organic solution obtained was washedsuccessively with a dilute aqueous solution of hydrochloric acid, withwater with an aqueous solution of sodium bicarbonate and again withwater. The solution was dried and concentrated to dryness and theresidue was dissolved in benzene. Then the solution was passed throughan alumina column and the eluate was concentrated to dryness to obtain2.74 gm. of dl-trans 3,3-dimethyl-2-cyclobutylidenemethyl 1cyclopropanecarboxylate of dlallethrolone having a refractive index n=l.5192. Analysis: C H O molecular weight=3l4.41. Calculated (percent)C, 76.40; H, 8.34. Found (percent): C, 76.1; H, 8.4.

Ultraviolet spectra (in ethanol) 1' max.: 224-225 m (s=21,200)

This compound is not described in the literature.

EXAMPLE XXIII Preparation of (5-benzyl-1-furyl-3)-methy1 dl-trans 3,3-dimethyl 2 cyclopentylidenemethyl-l-cyclopropanecarboxylate StepA.-Preparation of dl-trans3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acidchloride:

(1) Preparation of the sodium salt of the acid.1.08 gm. of dl-trans3,3-dimethyl-2-cyclopentylidenemethyl-lcyclopropanecarboxylic acid wasdissolved in 10 cc. of methanol containing 10% water and then sodiummethylate was added until alkaline reaction.

Next the methanol was eliminated by distillation under vacuum andbenzene was added and the mixture was again distilled in order tocompletely eliminate the water of the reaction whereby the sodium saltof dl-trans 3,3-dimethyl- 2-cyclopentylidenemethyl lcyclopropanecarboxylic acid was obtained.

This compound is not described in the literature.

(2) Preparation of the acid chloride.The sodium salt obtained in thepreceding step was suspended in 30 cc. of benzene and the reactionmixture was cooled after which 2 cc. of pyridine, followed by 4.7 cc. ofoxalyl chloride were added thereto. Next the reaction mixture wasagitated and the precipitate formed was eliminated by filtration andwashed with benzene. The benzene wash liquors were combined with theprincipal filtrate to obtain a henzene solution of dl-trans3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acidchloride which was used as such for the next step.

Step B.-Preparation of (5-benzyl-furyl-3)-methyl dltrans3,3-dimethyl-2-cyclopentylidene-methyl 1 cyclopropane carboxylate:

1.5 cc. of pyridine and 1.05 gm. of (5-benzyl-furyl-3)- methyl alcoholin a solution in 10 cc. of benzene were added to the benzene solution ofthe acid chloride obtained in the preceding. The reaction mixture wasagitated for 16 hours at room temperature and then water was added. Theorganic phase was separated by decanting. The aqueous phase wasextracted with ether and the combined organic phases were washedsuccessively with a cold aqueous solution of hydrochloric acid, withwater, with an aqueous solution of sodium bicarbonate and again withwater, dried and concentrated to dryness. The product thus obtained wasdissolved in benzene and the benzene solu tion was passed through analumina column and the eluate was concentrated to dryness to obtain1.234 gm. of benzyl-furyl-3)-methyl dl-trans 3,3dimethyl-Z-cyclopentylidenemethyl-1-cyclopropanecarboxylate having amelting point below 40 C. The product was in solid form at roomtemperature. Analysis: C H O molecular weight=364.46. Calculated(percent): C, 79.09; H, 7.74. Found (percent): C, 79.4; H, 8.0.

Ultraviolet spectra (in ethanol) 7\ max. at 207-208 m (e=24,000)

This compound is not described in the literature.

EXAMPLE XXIV Preparation of (5-benzyl-furyl-3)-methyl dl-trans 3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylate StepA.Preparation of dl-trans 3,3-dimethyl-2-cyclopentylidenemethyl-1-cyclopropanecarboxylic acid:

l-ephedrine was reacted with dl-trans 3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acid in the presence ofethyl acetate. A precipitate was isolated by vacuum filtration which,after purification, led to the lephedrine salt of d-trans3,3-dimethyl-Z-cyclopentylidenemethyl-l-cyclopropanecarboxylic acid(salt A) having a melting point of 162 C. and a specific rotation of[0L] =7 (c.=1.1% in chloroform).

By acidification of salt A, d-trans3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acidhaving a melting point of 60 C. (slightly pure) and a specific rotationof [a] =+2 (c.=1% in chloroform) (acid A was obtained.

From the filtrate (ethyl acetate solution) a product was obtained which,after purification, was the l-ephedrine salt of l-trans3,3-dimethyl-Z-cyclopentylidenesmethyl-loyclopropanecarboxylic acid(salt B) having a melting point of 112 C. and a specific rotation of[(2] ='13 (c.=1.1% in chloroform).

By acidification of salt B, l-trans3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acidhaving a melting point of 60 C. and a specific rotation of []D (c.=l% inchloroform) (acid B was obtained.

Although the rotatory power of the acids obtained may border on zero,resolution had definitely occurred. In fact, by ozonization of d-transchrysanthemic acid as well as by ozonization of acid A obtained from theephedrine salt having a melting point of 162 C., the same l-transcaronic acid was arrived at having a melting point of 212 C. and aspecific rotation of [a] -35 (c.=l.8% in methanol). [See H. Staudingerand L. Ruzicka, Helv. Chem. Acta 7, 201 (1924)].

The l-ephedrine salt of d-trans3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acid, the1- ephedrine salt of l-trans3,3-dimethyl-Z-cyclopentylidenemethyl-l-cyclopropanecarboxylic acid,d-trans 3,3-dimethyl-Z-cyclopentylidenemethyl 1 cyclopropanecarboxylicacid and l-trans 3,3-dimethyl-Z-cyclopentylidenemethyl-l-cyclopropanecarboxylic acid are not described in the literature.

Step B.--Preparation of d-trans3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acidchloride:

(1) Preparation of the sodium salt of the said acid. 1.14 gm. of d-trans3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acid weredissolved in 2 cc. of methanol and then sufficient 2.06 N methanolicsodium hydroxide solution was added until alkaline reaction. Themethanol was eliminated under reduced pressure and benzene was added tothe residue and the solution was again concentrated to dryness underreduced 30 pressure in order to entirely eliminate the water of thereaction whereby the sodium salt of d-trans 3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropane carboxylic acid was obtained.

This compound is not described in the literature.

(2) Preparation of the acid chloride.The sodium salt obtained in thepreceding step was suspended in 30 cc. of benzene and the reactionmixture was cooled. Under an atomsphere of nitrogen, first 2 cc. ofpyridine, then 4.7 cc. of oxalyl chloride were added to the reactionmixture which was then agitated and concentrated to dryness underreduced pressure. Then benzene was added to the residue and the reactionmixture was again concentrated to dryness to entirely eliminate thebenzene and oxalyl chlo ride. The precipitate formed was removed byfiltration and was washed with benzene and the benzene wash waters werecombined with the principal filtrate to obtain a benzene solution ofd-trans 3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylicacid chloride which was utilized as such for the next step.

Step C.-Preparation of (5-benzyl-furyl-3)-methyl dtrans3,3-dimethyl-2-cyclopentylidenemethyl-1 cyclopropanecarboxylate:

2 cc. of pyridine and 1.12 gm. of (5-benzyl-furyl-3)- methyl alcohol insolution in 10 cc. of benzene were added to the benzene solution ofd-trans acid chloride of Step 13 and the reaction mixture was agitatedfor 16 hours at room temperature and then diluted with water. Theorganic phase was separated by decanting and the aqueous phase wasextracted with ether and the ether phases were combined with the benzenesolution. The organic phase obtained was washed successively with a coldaqueous solution of hydrochloric acid, with water, with an aqueoussolution of sodium bicarbonate and again with water, then dried andconcentrated to dryness. The residue was dissolved in benzene and thebenzene solution obtained was passed through an alumina column and theeluate was concentrated to dryess to obtain 1.3 gm. of(S-benzylfuryl-3)-methyl d-trans3,3-dimethyl-2cyclopentylidenemethyl-l-cyclopropanecarboxylate having arefractive index n :1.5420. Analysis: C H O molecular weight=364.46.Calculated (percent): C, 79.09; H, 7.74. Found (percent): C, 79.1; H,7.7.

Ultraviolet spectra (in ethanol) 1' max. at 208 my (e=23,500)

This compound is not described in the literature.

EXAMPLE XXVTrans-3,3-dimethyl-2-cyclopentylidene-methyl-cyclopropane-l-carboxylicacid (1R,2R)

Step A.Trans-3,3-dimethy1-2-formyl-cyclopropane-1- carboxylic acid(1R,2R):

30 gm. of d-trans chrysanthemic acid (1R,2R) [obtained from d,1-transcis-chystzinthemic acid by crystallization of itsD()-threo-1-p-nitrophenyl-Z-dimethylaminopropane-1,3-diol salt asdescribed in copending, commonly assigned US. patent application Ser.No. 742,532, filed July 5, 1968, and entitled: Novel resolution process]were dissolved in 375 cc. of methanol and after cooling the solution to80 C., an ozonized oxygen current was bubbled through the solution untila blue color appeared. Then an oxygen current was bubbled through thesolution for 15 minutes followed by a nitrogen current for 45 minutes.15 cc. of dimethyl sulfide were slowly added to the solution and thereaction mixture was held for 30 minutes at -35 C., then for 1 hour at 0C. and finally 1 hour at room temperature. The methanol was removed bydistillation under reduced pressure and the residue was added to asolution of 25.5 gm. of trimethylamino-acetohydrazide chloride (reagentT) in 250 cc. of ethanol and 25 cc. of acetic acid. The reaction mixturewas heated to reflux and held there for one hour and then cooled. The

31 mixture was poured into a dilute solution of sodium hydroxide andthen was extracted with ether to remove any non-aldehyde fraction. Themixture was then made acidic with dilute aqueous hydrochloric acid andthe aqueous phase was extracted with ether.

The ether extracts were washed, dried and concentrated to dryness. Theresiduewas pasted with petroleum ether (boiling point=35-75 C.) toobtain 8.7 gm. of trans-3,3- dimethyl-2-formy1-cyclopropane-l-carboxylicacid (1R, 2R).

Step B.-Trans-3,3 dimethyl 2cyclopentylidenemethyl-cyclo-propane-l-carboxylic acid (1R,2R):

24.66 gm. of triphenyl-cyclopentylphosphonium bromide (prepared bymethod of Ramirez et al. J.A.C.S., vol. 79, 1957, p. 67) was added undera nitrogen atmosphere to 100 cc. of dimethoxyethane and then 97 cc. of a1.3 N solution of butyl lithium in hexane was progressively added to thereaction mixture. The mixture was stirred for 2 hours at roomtemperature and then a solution of 5.7 gm. oftrans-3,3-dimethyl-2450rmyl-cyclopropane-l-carboxylic acid (1R,2R) in 30cc. of dimethoxyethane was added thereto with stirring at a temperatureless than 60 C. The mixture was stirred for 2 hours at 60 C., cooled andthen concentrated to dryness by distillation under reduced pressure. Theresidue was added to water with stirring and the aqueous mixture wasextracted with ether. The ether extracts were discarded and the aqueousphase was adjusted to a pH of 4.7 with dilute hydrochloric acid. Theaqueous acid phase Was extracted with ether and the ether extract waswashed with water, dried and concentrated to dryness under reducedpressure. The oily residue was added to gm. of reagent T in 100 cc. ofethanol and cc. of acetic acid. The reaction mixture was heated toreflux and held there for 1 hour. After cooling, the mixture was madealkaline with aqueous sodium hydroxide and was extracted with ether. Thecombined ether extracts were dried and evaporated to dryness to obtain3.85 gm. of crude acid.

The crude acid was dissolved in 11 cc. of ethyl acetate and a solutionof 3.2 gm. of l-ephedrine in 11 cc. of ethyl acetate was added thereto.After standing, the mixture was vacuum filtered to obtain 5.55 gm. ofl-ephedrine salt oftrans-3,3-dimethyl-2-cyclopentylidene-methyl-cyclopropane-Lcarboxylicacid (1R,2R) melting at 158 C. and after recrystallization from ethylacetate melting at 160 C. and having a specific rotation [a] =6(c.=0.25% in chloroform).

The said product was then made acidic by addition to aqueous dilutehydrochloric acid and the acid aqueous phase was extracted with ether.The ether phase was washed with water, dried and distilled to drynessunder reduced pressure. A small amount of petroleum ether was added tothe residue to cause crystallization of 2.70 gm. oftrans-3,3-dimethyl-Z-cyclopentylidene-methyl-cyclopropane-l-carboxylicacid (1R,2R) melting at about C. and having a specific rotation [a] =-|5(c.=0.35% in chloroform).

N.M.R. spectrum (deuterochloroform) carboxyl EXAMPLE XXVI l-transchrysanthemic acid (lS,2S) was obtained from dl-trans-cis chrysanthemicacid by precipitation of its L(+)threo-l-p-nitrophenyl-Z-dimethylaminopropane-1, 3-diol salt thereof asdescribed in copending, commonly assigned US. patent application Ser.No. 742,532, filed 32 July 5, 1968, and entitled, Novel ResolutionProcess. Using the procedure of Step A of Example XXV, l-transchrysanthemic acid (lS,2S) was reacted to obtain trans-3,3-dimethyl-Z-formyl-cyclopropane-l-carboxylic acid (18, 2S).

Using the procedure of Step B of Example XXV, trans- 3,3 dimethyl 2formyl-cyclopropane-l-carboxylic acid (lS,2S) was reacted to formtrans-3,3-dimethyl-2-cyclopentylidene-methyl-cyclopropane-l-carboxylicacid (IS, 28) having a specific rotation [a] =O (c.=1% in chloroform).The product was identical to that described above under the name of1-trans-3,3-dimethyl-2-cyclo pentylidene methyl cyclopropanel-carboxylic acid or acid B EXAMPLE XXVIITrans-3,3-dimethyl-Z-cyclopentylidenemethyl-cyclopropane-l-carboxylicacid (1R,2R)

86.5 gm. of triphenylcyclopentyl-phosphonium bromide was added under anitrogen atmosphere to 350 cc. of dimethoxy-ethane and then 340 cc. of a1.3 N solution of butyl lithium in hexane was added thereto. Thereaction mixture was stirred for 2 hours at room temperature and then asolution of 20 gm. oftrans-3,3-dimethyl-2-formylcyclopropane-l-carboxylic acid (1R,2R) in 105cc. of dimethoxyethane was added thereto at a temperature not above 60C. The reaction mixture was stirred at 60 C. for 2 hours and then cooledand evaporated to dryness under reduced pressure. The residue was addedto water with stirring and the aqueous mixture was extracted with ether.The ether extracts were discarded and the aqueous phase was madeadjusted to a pH of 4.7 with dilute hydrochloric acid. The acid aqueousphase was extracted with ether and the combined ether extracts werewashed with water, dried and evaporated to dryness under reducedpressure. The oily residue was admixed with cc. of ethyl acetate. Themixture was vacuum filtered and the precipitate was washed with ethylacetate to obtain 21 gm. of crude acid.

The crude acid was added to a solution of 22.5 gm. of l-ephedrine in cc.of ethyl acetate and the mixture was allowed to stand to eifectcrystallization. The mixture was vacuum filtered and the precipitate waswashed with ethyl acetate and dried to obtain 27 gm. of l-ephedrine saltof trans 3,3dimethyl-2-cyclopentylidene-methyl-cyclopropane-l-carboxylic acid(1R,2R) melting at C. and having a specific rotation [a] =-5.5 (c.=0.35%in chloroform). The said salt was acidified as in Example XXV to obtainalmost a quantitative yield of trans-3,3- dimethyl2-cyclopentylidene-methyl-cyclopropane-l-carboxylic acid (1R,2R), withrespect to the ephedrine salt.

EXAMPLE XXVIIITrans-3,3-dimethyl-Z-cyclopentylidene-methyl-cyclopropane-l-carboxylicacid (1R,2R)

Step A.Methyltrans-3,3-dimethyl-2-cyclopentylidenemethyl-cyclopropanel-carboxylate(1R,2R)

53 gm. of triphenylcyclopentylphosphonium bromide were added under inertatmosphere to 160 cc. of dimethyl sulfoxide to which was then added 11.6gm. of sodium methylate. After stirring the reaction mixture for onehour at room temperature, 13.4 gm. of the methyl ester of trans 3,3dimethyl-2-formyl-cyclopropane-l-carboxylic acid (1R,2R) [obtained asdescribed in copending US. patent application Ser. No. 841,140 filedJuly 11, 1969] were added to the reaction mixture over 30 minutes andthe mixture was then stirred for 21 hours at room temperature. Thereaction was poured into an ice-aqueous hydrochloric acid andcyclohexane was added thereto. The mixture was stirred, filtered toeliminate triphenyl-phosphine and the organic phase was decanted off.The aqueous phase was extracted with cyclohexane and the organic phaseswere combined, washed successively with water, with aqueous sodiumbicarbonate and then water, dried and evaporated to dryness underreduced pressure. The

33 residue was redistilled to obtain 17.29 gm. of methyl trans 3,3dimethyl-2-cyclopentylidene-methyl-cyclopropane-l-carboxylate (1R,2R)boiling at 82 C. at 0.5 mm. Hg and having a specific rotation [u](c.-=l% in chloroform). The saponification index was 271 mg. (269theoretical) of potassium hydroxide per gm.

The N.M.R. spectrum (in deutero chloroform) has the followingcharacteristics:

Peaks at 43-44 Hz. corresponding to hydrogen at position 1;

Peaks at 7077 Hz. corresponding to the methyl hydrogens at position 3;

Peaks a1 95-105 and 130-140 Hz. corresponding to the hydrogens of thecyclopentane cycle;

Peaks at 227 Hz. corresponding to methyl hydrogen of the methoxycarbonyl radical,

Peaks at 2555-3055 Hz. corresponding to the methyl hydrogen of thecyclopentylidene methyl radical.

StepB.--trans-3,3-dimethyl-2-cyclopentylidene-methylcyclopropane-l-carboxylicacid (1R,2R):

gm. of the product of Step A was added under inert atmosphere to amixture of 10 cc. of methanol and 10 cc. of water and 5 cc. of anaqueous solution of 10 N potassium hydroxide was added thereto. Thereaction mixture was heated at reflux for 1% hours and the methanol wasdistilled off at atmospheric pressure. Water and isopropyl ether wereadded to the reaction mixture which was then made acidic with aqueoushydrochloric acid. The organic phase was decanted off and the aqueousphase was extracted with isopropyl ether. The combined organic phaseswere washed with water and then evaporated to dryness under reducedpressure to obtain 9.25 gm. oftrans-3,3-dimethy1-2-eyclopentylidene-methyl-cyclopropane-l-carboxylicacid (1R,2R) having a specific rotation [a] =+5 (c.=0.35% inchloroform).

N.M.R. spectrum (deuterochlorofonn) The N.M.R. spectrum has thefollowing characteristics:

Peaks at 71 and 79 Hz. corresponding to the methyl hydrogens at 3;

Peaks at 82.5 and 87.5 Hz. corresponding to the hydrogen in position 1(doublet);

Peaks at 100 and 135 Hz, corresponding to the hydrogens of thecyclopentane cycle,

Peaks at 695 Hz. corresponding to the carboxyl hydrogen.

In an analogous way, starting from the methyl esters oftrans-3,3-dimethyl-2-formyl-cyclopropane-l-carboxylic (18,28) or racemicacids,trans-3,3-dimethyl-2-cyclopentylidenemethyl-cyclopropane-l-carboxylic(18,28) or racemic acids were obtained.

EXAMPLE XXIX Trans-3,3-dimethyl-2-(2-ethyl-1'-butenyl)-cyclopropane-l-carboxylic acid (1R,2R)

Step A.-Methyl ester of trans-3,3-dimethyl-2-(2'-e yl-lbutenyl)-cyclopropane-1-carboxylic acid (lR,2R):

23 gm. of triphenyl-3-pentyl-phosphonium iodide were added under aninert atmosphere to 200 cc. of benzene and 29.8 cc. of 1.68 N hexanesolution of butyl lithium was added thereto. The mixture was stirred for2 hours at room temperature and then a solution of 9.15 gm. of methyltrans 3,3-dimethyl-2-formyl-cyclopropane-l-carboxylate (1R,2R) in 20 cc.of benzene was slowly added thereto and then stirred for 2 hours at roomtemperature. After the addition of water, the reaction mixture wasfiltered to remove insolubles and the organic phase was decanted off.The aqueous phase was extracted with ether and the organic phases werecombined, dried and concentrated to dryness under reduced pressure. Theresidue was added to petroleum ether B.P.-=67-75 C. and the mixture wasfiltered to remove triphenyl phosphine oxide. The filtrate wasevaporated to dryness under reduced pres- 34 sure to obtain 9.67 gm. ofmethyl trans-3,3-dimethyl-2- (2' ethyl 1' butenyl) cyclopropane 1carboxylate (1R,2R).

Step B.Trans-3,3-dimethyl-2-(2' ethyl- -butenyl)-cyclopropane-l-carboxylic acid (lR,2R):

9.67 gm. of the product of Step A was added under an inert atmosphere toa mixture of 35 cc. of 2 N aqueous sodium hydroxide and 70 cc. ofmethanol and the reaction mixture was heated to reflux and was heldthere for 2 hours. The methanol was distilled off and water was addedthereto. The aqueous phase was extracted with ether and the ether phasewas removed. The aqueous phase was made acidic with aqueous hydrochloricacid. The ether phases were combined, dried and evaporated to dryness.The residue was redistilled under reduced pressure and the middlefraction of 5.87 gm. and having a boiling point of 96 C. at 0.15 mm. Hgwas dissolved in 50 cc. of ethanol and 5 cc. of acetic acid. 5 gm. ofReagent T was added to the reaction mixture which was then heated toreflux and held there for 1% hours. After cooling the reaction mixturewas poured into dilute aqueous sodium hydroxide and the mixture wasextracted with ether. The ether phases were dried and evaporated todryness to obtain 5.03 gm. of trans-3,3-dimethyl-2-(2'- ethyl-'-butenyl)-cyclopropane-1carboxylic acid (1R,2R) having a specificrotation [u] =+28.5 (cs-1.4% in ethanol).

U.V. spectrum (ethanol) Max. at 200-201 nm. (E}?,, =611) N.M.R. spectrum(deuterochloroform) The N.M.R. spectrum showed the followingcharacteristic:

Peaks at 51.5-59-66 Hz. corresponding to the methyl hydrogens of the2'-ethyl-butenyl radical,

Peaks at 69-78.5 Hz. corresponding to the methyl hydrogens at position3,

Peaks at 81-86 Hz. corresponding to the hydrogen at position 1,

Peaks at 124 Hz. corresponding to the CH, of the 2'- ethyl-butenylradical;

Peaks at 287-295 Hz. corresponding to the ethylene hydrogen of thebutenyl radical;

Peaks at 676 Hz. corresponding to the carboxyl hydrogen.

Various modifications of the process of the invention may be madewithout departing from the spirit or scope thereof and it is to beunderstood that the invention is to be limited only as defined in theappended claims.

What is claimed is:

1. A compound selected from the group consisting of racemic oroptionally-active cyclopropane carboxylic derivative having the formulaZ COT wherein Z and 2 are selected from the group consisting of loweralkyl having from 1 to 7 carbon atoms and phenyl and Z and Z togetherrepresent an alkylene residue having 4 to 5 carbon atoms, T is OT, Tbeing (5- benzylfuryl-3)-methyl, R and R are selected from the groupconsisting of lower alkyl and phenyl and may together represent analkylene residue having 3 to 7 carbon atoms which may be interrupted byan heteroatom selected from the group consisting of nitrogen and oxygenand which may be substituted by at least one substituent selected fromthe group consisting of lower alkyl and lower alkoxy, R is selected fromthe group consisting of hydrogen and lower alkyl or form together withR, an alkylene residue of 2 to 5 carbon atoms which may be unsaturatedor substituted by a hydrocarbon chain; with the proviso that when Z andZ are methyl and R is hydrogen, R is other than methyl.

2. A compound of claim 1 wherein R is hydrogen in trans configuration inrelation to the carboxylic chain and R and R together form an alkylideneof 2 to 5 carbon atoms.

3. A compound of claim '2 wherein R and R together form a butylidenechain.

4. A compound of claim 1 which is the (S-benzylfuryl- 3)-methyl ester ofdl-trans 3,3-dimethyl 2 cyclopentylidene-methyl-cyclopropanecarboxylicacid. 1

5. A compound of claim 1 selected from the group consisting of thedl-trans and an optically active form of the (5-benzyl-furyl-3) 'methylester of 3,3-di-methyl- 2cyclopentylidenemethyl-l-cyclopropanecarboxylic acid. 6. ,A compound ofclaim 1 which is the (S-benzyl-furyl- 3) methyl ester of d-trans3,3-dimethyl-2-cyclopentylidenernethyl-l-cyclopropanecarboxylic acid.

References Cited UNITED STATES PATENTS OTHER REFERENCES Staudinger,Helv. Chim. Acta, vol. 7, p. 390 (1924).

La Forge, J. Org. Chem., vol. 17, p. 381 (1962).

Lhoste, C. R., Agr. Fr. (1967), p. 686.

Cantu et al., J. Econ. Entomol., vol. 63, pp. 1373-4 (1970).

JOHN D. RANDOLPH, Primary Examiner US. Cl. X.R.

260345.9, 347. 3, 347.4, 468 P, 514 P, 544 L, 607 A, 617 R, 618 R, 631R, 638 B, 648 R, 654 R; 424285, 306

WD STATES PATENT CERTIFICATE OF CORRECTION Intent No. 3,7 5 DatedJanuary 15, 197 4 m JACQUES MARTEL, CHANH HUY'NH, and JEAN BUENDIA It 1.certified that error appears in the above-identified patent and that:aid Letters Pagan: are hereby corrected as shmm below 2301. Line Page L5 i qrf Asfsigne ROUSSE L UCLAfi;

' 1 Pgris, Frence I 57 11 ,l'T" "pzpeessw-should be 'pf'ocese s 6 35 1 L3 the formul a I I H H Trans isomer Cis, isomer 6 +9 1M 1o-"I"1onwithsta.nding" should be notwithstanding 6 55 1 1 1 the formula.

should be p33 UNITED sm'mas PATERT OFFICE CERTIFICATE OF CORRECTION 1mmNo. 3,7 6,052 new: January 15, 9?

mad) JACQUES MARTEL, CILANII HUYNH, and JEAN BUENDIA It 1! certifiedthat error appears in the above-identified patent ed the: ma LettersPatent are hereby corrected gs shown belows- 601. Li-rie Page Line 1 A j9 21a 1" "0] should be i gm 6' 32 e 23 9 "ref-lectiv 'e should 'be refrag ztiv e 60- 28 ",as should be": was 2 I 1 L3 32 3O 6 I "pentenyl"should be pentenyl 4 .1 33 7-8 "3,3-dimethyl2-2' "should be f-- e 6 -33-dimebhyl-2(2'- Y 53 35 21 ".the should be .The 1 16 37 2 "chlorides"should be chlox 'ide 16 39 37 19. "l -2" should be 1.2 6 18 42 1o"225236" should be 225-226 7 l9 m 6 "cyclopropanecarboxylic" should becyclopropanecarboxylate 20 2 61-62 +8 17-18"(2'6'-dimethyl-cyclopropa.necarboxylic" should be (2, '6'--dimethyl--cyclohexylidene-methyl) -cyelopropane-carboxylic 22 ll 52 15 "phenylsulfone produced" should be p-tolyl sulfone prepared 22 +7 52 22 "n 5"should be n 61 53 5 "phenyl sulfone produced" should be p-tolyl sulfoneprepared 3 '1 5 28 "cyclobutylidenemthyl" should becyclobutylidenemethyl 24 2O 56 19 "equeous" should be aqueous

